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A.h. Penninks - One of the best experts on this subject based on the ideXlab platform.

  • The thymus atrophy inducing Organotin Compound DBTC stimulates TCRalfabeta-CD3 signalling in immature rat thymocytes
    Biochemical and biophysical research communications, 1995
    Co-Authors: Raymond Pieters, Marianne Bol, Willem Seinen, P. Punt, J.m. Van Dijken, A.h. Penninks
    Abstract:

    In the present study, we show that the thymus atrophy inducing Compound DBTC stimulates the intracellular release, but not the influx, of Ca2+ elicited by cross-linking of the TcRαβ-CD3-complex on rat thymocytes and inhibits capping of TcRαβ. Similarities with the effects of cytochalasin B together with the finding that DBTC also inhibited capping of CD8, whereas cross-linking of CD8 did not cause a Ca2+-response, suggest that DBTC interferes with TcRαβ-CD3-signalling by selective interference with cytoskeletal functioning. The responding thymocytes were CD53- and FSC(low), thus possibly including the non proliferating counterpart of the presumed immature CD4-CD8+CD53- target cells of DBTC. The present effects may therefore relate to the mechanisms of Organotin-induced thymus atrophy.

  • The thymus atrophy-inducing Organotin Compound dbtc inhibits the binding of thymocytes to thymic epithelial cells
    International journal of immunopharmacology, 1995
    Co-Authors: Raymond Pieters, Willem Seinen, N.j. Snoeij, Ruud Albers, Rob Bleumink, Tsunetoshi Itoh, A.h. Penninks
    Abstract:

    Abstract In this study, it is examined whether the Organotin Compound di-n-butyltindichloride (DBTC), which has been shown to inhibit immature thymocyte proliferation, is able to disturb the binding between thymocytes and thymic epithelial cells (TEC). To that end, an enzyme-linked binding assay was developed in which the amount of binding of Thy-1 + (mAb ER4)-thymocytes to the rat-derived TEC-line IT45R1 (IT45R1-TEC) could be detected. It was found that preincubation of thymocytes with 3–5 μM DBTC for 30 min inhibited the binding by 50–60% during a 1 h adhesion period. By extending the preincubation period to 1 h and the adhesion period to 22 h, 0.1 μM DBTC was already sufficient to reduce the binding with 60–80%. Further characterization of the binding revealed that splenic lymphocytes were unable to bind to the MHC class II-negative IT45R1-TEC. Since dextran sulfate inhibited the binding as well, sulfated polysaccharide-binding molecules such as Thy-I and CD2 are likely to be involved in the binding. Electron microscopy showed filament-containing microvilli at the site of interaction. The results are discussed in relation to the mechanism of DBTC-induced thymus atrophy.

  • Selective inhibition of immature CD4-CD8+ thymocyte proliferation, but not differentiation, by the thymus atrophy-inducing Compound di-n-butyltin dichloride.
    Immunology, 1994
    Co-Authors: Raymond Pieters, Marianne Bol, Willem Seinen, P. Punt, T. Ariëns, Nanne Bloksma, A.h. Penninks
    Abstract:

    Effects of the thymus atrophy-inducing Organotin Compound di-n-butyltin dichloride (DBTC) on the differentiation and proliferation of immature rat thymocyte subsets were studied in vivo and in vitro. Incubation of freshly isolated CD4-CD8- or immature CD4-CD8+ (characterized as CD4-CD53-) thymocytes with 10(-7) M DBTC for 18 hr did not affect cell recovery or their ability to differentiate to CD4-CD8+ cells and CD4+CD8+ or to CD4+CD8+ cells, respectively. The same treatment decreased the spontaneous as well as the phytohaemagglutinin (PHA)-induced proliferation in both subsets. However, the inhibition of proliferation by DBTC of immature CD4-CD8+, but not of CD4-CD8- thymocytes, appeared to increase with their growth rate. Data show that differentiation of immature thymocytes can proceed independently of proliferation and that DBTC causes thymus atrophy by selectively inhibiting the proliferation of immature CD4-CD8+ thymocytes. Administration to rats of DBTC via the diet for 14 days resulted in an initial decrease of thymoblast number by day 2, followed by a decrease in the total number of thymocytes by day 4. Total thymocyte numbers were lowest on day 7 and did not significantly change thereafter. CD4/CD8 thymocyte subset distributions were similar to controls on day 4, but on day 7 of feeding a marked reduction of the percentage of CD4+CD8+ thymocytes and consequently an increase of the percentages of the three other CD4/CD8 subsets were found. Thereafter, the CD4/CD8 subset distribution recovered, reaching near control values on day 14, despite the very low numbers of thymoblasts and of total thymocytes at that time. Data together indicate that DBTC reduces the production of CD4+CD8+ and mature single-positive thymocytes by selectively inhibiting immature CD4-CD8+ thymocyte proliferation but without affecting the differentiation capacity of these cells. This suggests that thymocyte proliferation and differentiation are separately regulated processes.

  • Recovery from chemically induced thymus atrophy starts with CD4- CD8- CD2high TcR alpha beta-/low thymocytes and results in an increased formation of CD4- CD8- TcR alpha beta high thymocytes.
    Immunology, 1993
    Co-Authors: Raymond Pieters, B. W. Lam, Marianne Bol, Willem Seinen, Nanne Bloksma, A.h. Penninks
    Abstract:

    Regeneration of the thymus was studied in rats that were treated with a single oral dose of the Organotin Compound di-n-butyltin dichloride (DBTC). After an initial maximum depletion of cortical BrdU+ thymocytes on day 2 after treatment, repopulation appeared to start on day 3 as indicated by an increased number of BrdU+ cells in the subcapsular region. On day 5, when thymocyte depletion was most pronounced, a relative increase of BrdU+ cells was observed all over the cortex. In comparison with controls, the thymoblast population on day 5 appeared to harbour increased numbers of CD4- CD8- and immature CD4- CD8+ CD53- thymoblasts, while the number of CD4+ CD8+ blasts had decreased. In comparison with day 3, however, the number of CD4+ CD8+ blasts had increased again. Results together have been interpreted as indicative for thymus regeneration starting from CD4- CD8- blasts which differentiate to immature CD4- CD8+ and then to CD4+ CD8+ blasts. Further characterization revealed that the majority of the CD4- CD8- and CD4- CD8+ CD53- blasts expressed high levels of CD2 and no or low levels of T-cell receptor (TcR) alpha beta. The high expression of CD2 on repopulating thymoblasts may be an additional indication of their activated state and for a role of interaction with the ligand LFA-3 on thymic epithelial cells during this phase of thymocyte differentiation. The number of CD4- CD8- TcR alpha beta high cells was increased on day 5 after dosing. The origin of this population and the possible implication of its development during thymus regeneration after chemically induced thymus atrophy are discussed.

  • The Organotin-induced thymus atrophy, characterized by depletion of CD4+ CD8+ thymocytes, is preceded by a reduction of the immature CD4- CD8+ TcR alpha beta-/low CD2high thymoblast subset.
    Immunology, 1992
    Co-Authors: Raymond Pieters, B. W. Lam, Marianne Bol, Willem Seinen, A.h. Penninks
    Abstract:

    Thymic changes in the rat induced by the thymus atrophy-inducing Organotin Compound di-n-butyltin dichloride (DBTC) were examined using FACS analyses. The number of CD4+CD8+ thymocytes was reduced by DBTC treatment from Day 2 onwards and reached minimum level on Days 4 and 5 after dosing. On these days the CD4-CD8- and both the CD4-CD8+ and CD4+CD8- subsets were not affected. On Day 2 we observed a reduced proportion of transferrin receptor (CD71)-positive CD4-OX44- cells, representing the cycling immature CD4-CD8+ cells, and of CD71+OX44- cells, representing the cycling CD4+CD8+ cells, but not of CD71+CD4-CD8- cells. When compared to controls, the FSChigh cell population of DBTC-treated rats contained less CD4-OX44- and OX44- cells, which were further characterized as CD2high and T-cell receptor (TcR)alpha beta- low. Moreover, fewer TcR alpha beta high cells were detected in the OX44- thymoblast subset of DBTC-treated rats. The number of CD4-CD8- thymoblasts appeared marginally decreased while the numbers of CD4+OX44+ cells, representing mature CD4+ cells, were not affected. These data indicate that DBTC causes a preferential initial depletion of immature CD4-CD8+CD2high TcR alpha beta-low thymoblasts. This initial event may result in a decreased formation of CD4+CD8+ thymoblasts and of small CD4+CD8+ thymocytes. These characteristics of the initially depleted subset indicate a specific anti-proliferative effect of DBTC and may give clues for the mechanism involved in the induction of thymus atrophy.

Raymond Pieters - One of the best experts on this subject based on the ideXlab platform.

  • The thymus atrophy inducing Organotin Compound DBTC stimulates TCRalfabeta-CD3 signalling in immature rat thymocytes
    Biochemical and biophysical research communications, 1995
    Co-Authors: Raymond Pieters, Marianne Bol, Willem Seinen, P. Punt, J.m. Van Dijken, A.h. Penninks
    Abstract:

    In the present study, we show that the thymus atrophy inducing Compound DBTC stimulates the intracellular release, but not the influx, of Ca2+ elicited by cross-linking of the TcRαβ-CD3-complex on rat thymocytes and inhibits capping of TcRαβ. Similarities with the effects of cytochalasin B together with the finding that DBTC also inhibited capping of CD8, whereas cross-linking of CD8 did not cause a Ca2+-response, suggest that DBTC interferes with TcRαβ-CD3-signalling by selective interference with cytoskeletal functioning. The responding thymocytes were CD53- and FSC(low), thus possibly including the non proliferating counterpart of the presumed immature CD4-CD8+CD53- target cells of DBTC. The present effects may therefore relate to the mechanisms of Organotin-induced thymus atrophy.

  • The thymus atrophy-inducing Organotin Compound dbtc inhibits the binding of thymocytes to thymic epithelial cells
    International journal of immunopharmacology, 1995
    Co-Authors: Raymond Pieters, Willem Seinen, N.j. Snoeij, Ruud Albers, Rob Bleumink, Tsunetoshi Itoh, A.h. Penninks
    Abstract:

    Abstract In this study, it is examined whether the Organotin Compound di-n-butyltindichloride (DBTC), which has been shown to inhibit immature thymocyte proliferation, is able to disturb the binding between thymocytes and thymic epithelial cells (TEC). To that end, an enzyme-linked binding assay was developed in which the amount of binding of Thy-1 + (mAb ER4)-thymocytes to the rat-derived TEC-line IT45R1 (IT45R1-TEC) could be detected. It was found that preincubation of thymocytes with 3–5 μM DBTC for 30 min inhibited the binding by 50–60% during a 1 h adhesion period. By extending the preincubation period to 1 h and the adhesion period to 22 h, 0.1 μM DBTC was already sufficient to reduce the binding with 60–80%. Further characterization of the binding revealed that splenic lymphocytes were unable to bind to the MHC class II-negative IT45R1-TEC. Since dextran sulfate inhibited the binding as well, sulfated polysaccharide-binding molecules such as Thy-I and CD2 are likely to be involved in the binding. Electron microscopy showed filament-containing microvilli at the site of interaction. The results are discussed in relation to the mechanism of DBTC-induced thymus atrophy.

  • Selective inhibition of immature CD4-CD8+ thymocyte proliferation, but not differentiation, by the thymus atrophy-inducing Compound di-n-butyltin dichloride.
    Immunology, 1994
    Co-Authors: Raymond Pieters, Marianne Bol, Willem Seinen, P. Punt, T. Ariëns, Nanne Bloksma, A.h. Penninks
    Abstract:

    Effects of the thymus atrophy-inducing Organotin Compound di-n-butyltin dichloride (DBTC) on the differentiation and proliferation of immature rat thymocyte subsets were studied in vivo and in vitro. Incubation of freshly isolated CD4-CD8- or immature CD4-CD8+ (characterized as CD4-CD53-) thymocytes with 10(-7) M DBTC for 18 hr did not affect cell recovery or their ability to differentiate to CD4-CD8+ cells and CD4+CD8+ or to CD4+CD8+ cells, respectively. The same treatment decreased the spontaneous as well as the phytohaemagglutinin (PHA)-induced proliferation in both subsets. However, the inhibition of proliferation by DBTC of immature CD4-CD8+, but not of CD4-CD8- thymocytes, appeared to increase with their growth rate. Data show that differentiation of immature thymocytes can proceed independently of proliferation and that DBTC causes thymus atrophy by selectively inhibiting the proliferation of immature CD4-CD8+ thymocytes. Administration to rats of DBTC via the diet for 14 days resulted in an initial decrease of thymoblast number by day 2, followed by a decrease in the total number of thymocytes by day 4. Total thymocyte numbers were lowest on day 7 and did not significantly change thereafter. CD4/CD8 thymocyte subset distributions were similar to controls on day 4, but on day 7 of feeding a marked reduction of the percentage of CD4+CD8+ thymocytes and consequently an increase of the percentages of the three other CD4/CD8 subsets were found. Thereafter, the CD4/CD8 subset distribution recovered, reaching near control values on day 14, despite the very low numbers of thymoblasts and of total thymocytes at that time. Data together indicate that DBTC reduces the production of CD4+CD8+ and mature single-positive thymocytes by selectively inhibiting immature CD4-CD8+ thymocyte proliferation but without affecting the differentiation capacity of these cells. This suggests that thymocyte proliferation and differentiation are separately regulated processes.

  • Recovery from chemically induced thymus atrophy starts with CD4- CD8- CD2high TcR alpha beta-/low thymocytes and results in an increased formation of CD4- CD8- TcR alpha beta high thymocytes.
    Immunology, 1993
    Co-Authors: Raymond Pieters, B. W. Lam, Marianne Bol, Willem Seinen, Nanne Bloksma, A.h. Penninks
    Abstract:

    Regeneration of the thymus was studied in rats that were treated with a single oral dose of the Organotin Compound di-n-butyltin dichloride (DBTC). After an initial maximum depletion of cortical BrdU+ thymocytes on day 2 after treatment, repopulation appeared to start on day 3 as indicated by an increased number of BrdU+ cells in the subcapsular region. On day 5, when thymocyte depletion was most pronounced, a relative increase of BrdU+ cells was observed all over the cortex. In comparison with controls, the thymoblast population on day 5 appeared to harbour increased numbers of CD4- CD8- and immature CD4- CD8+ CD53- thymoblasts, while the number of CD4+ CD8+ blasts had decreased. In comparison with day 3, however, the number of CD4+ CD8+ blasts had increased again. Results together have been interpreted as indicative for thymus regeneration starting from CD4- CD8- blasts which differentiate to immature CD4- CD8+ and then to CD4+ CD8+ blasts. Further characterization revealed that the majority of the CD4- CD8- and CD4- CD8+ CD53- blasts expressed high levels of CD2 and no or low levels of T-cell receptor (TcR) alpha beta. The high expression of CD2 on repopulating thymoblasts may be an additional indication of their activated state and for a role of interaction with the ligand LFA-3 on thymic epithelial cells during this phase of thymocyte differentiation. The number of CD4- CD8- TcR alpha beta high cells was increased on day 5 after dosing. The origin of this population and the possible implication of its development during thymus regeneration after chemically induced thymus atrophy are discussed.

  • The Organotin-induced thymus atrophy, characterized by depletion of CD4+ CD8+ thymocytes, is preceded by a reduction of the immature CD4- CD8+ TcR alpha beta-/low CD2high thymoblast subset.
    Immunology, 1992
    Co-Authors: Raymond Pieters, B. W. Lam, Marianne Bol, Willem Seinen, A.h. Penninks
    Abstract:

    Thymic changes in the rat induced by the thymus atrophy-inducing Organotin Compound di-n-butyltin dichloride (DBTC) were examined using FACS analyses. The number of CD4+CD8+ thymocytes was reduced by DBTC treatment from Day 2 onwards and reached minimum level on Days 4 and 5 after dosing. On these days the CD4-CD8- and both the CD4-CD8+ and CD4+CD8- subsets were not affected. On Day 2 we observed a reduced proportion of transferrin receptor (CD71)-positive CD4-OX44- cells, representing the cycling immature CD4-CD8+ cells, and of CD71+OX44- cells, representing the cycling CD4+CD8+ cells, but not of CD71+CD4-CD8- cells. When compared to controls, the FSChigh cell population of DBTC-treated rats contained less CD4-OX44- and OX44- cells, which were further characterized as CD2high and T-cell receptor (TcR)alpha beta- low. Moreover, fewer TcR alpha beta high cells were detected in the OX44- thymoblast subset of DBTC-treated rats. The number of CD4-CD8- thymoblasts appeared marginally decreased while the numbers of CD4+OX44+ cells, representing mature CD4+ cells, were not affected. These data indicate that DBTC causes a preferential initial depletion of immature CD4-CD8+CD2high TcR alpha beta-low thymoblasts. This initial event may result in a decreased formation of CD4+CD8+ thymoblasts and of small CD4+CD8+ thymocytes. These characteristics of the initially depleted subset indicate a specific anti-proliferative effect of DBTC and may give clues for the mechanism involved in the induction of thymus atrophy.

Willem Seinen - One of the best experts on this subject based on the ideXlab platform.

  • The thymus atrophy inducing Organotin Compound DBTC stimulates TCRalfabeta-CD3 signalling in immature rat thymocytes
    Biochemical and biophysical research communications, 1995
    Co-Authors: Raymond Pieters, Marianne Bol, Willem Seinen, P. Punt, J.m. Van Dijken, A.h. Penninks
    Abstract:

    In the present study, we show that the thymus atrophy inducing Compound DBTC stimulates the intracellular release, but not the influx, of Ca2+ elicited by cross-linking of the TcRαβ-CD3-complex on rat thymocytes and inhibits capping of TcRαβ. Similarities with the effects of cytochalasin B together with the finding that DBTC also inhibited capping of CD8, whereas cross-linking of CD8 did not cause a Ca2+-response, suggest that DBTC interferes with TcRαβ-CD3-signalling by selective interference with cytoskeletal functioning. The responding thymocytes were CD53- and FSC(low), thus possibly including the non proliferating counterpart of the presumed immature CD4-CD8+CD53- target cells of DBTC. The present effects may therefore relate to the mechanisms of Organotin-induced thymus atrophy.

  • The thymus atrophy-inducing Organotin Compound dbtc inhibits the binding of thymocytes to thymic epithelial cells
    International journal of immunopharmacology, 1995
    Co-Authors: Raymond Pieters, Willem Seinen, N.j. Snoeij, Ruud Albers, Rob Bleumink, Tsunetoshi Itoh, A.h. Penninks
    Abstract:

    Abstract In this study, it is examined whether the Organotin Compound di-n-butyltindichloride (DBTC), which has been shown to inhibit immature thymocyte proliferation, is able to disturb the binding between thymocytes and thymic epithelial cells (TEC). To that end, an enzyme-linked binding assay was developed in which the amount of binding of Thy-1 + (mAb ER4)-thymocytes to the rat-derived TEC-line IT45R1 (IT45R1-TEC) could be detected. It was found that preincubation of thymocytes with 3–5 μM DBTC for 30 min inhibited the binding by 50–60% during a 1 h adhesion period. By extending the preincubation period to 1 h and the adhesion period to 22 h, 0.1 μM DBTC was already sufficient to reduce the binding with 60–80%. Further characterization of the binding revealed that splenic lymphocytes were unable to bind to the MHC class II-negative IT45R1-TEC. Since dextran sulfate inhibited the binding as well, sulfated polysaccharide-binding molecules such as Thy-I and CD2 are likely to be involved in the binding. Electron microscopy showed filament-containing microvilli at the site of interaction. The results are discussed in relation to the mechanism of DBTC-induced thymus atrophy.

  • Selective inhibition of immature CD4-CD8+ thymocyte proliferation, but not differentiation, by the thymus atrophy-inducing Compound di-n-butyltin dichloride.
    Immunology, 1994
    Co-Authors: Raymond Pieters, Marianne Bol, Willem Seinen, P. Punt, T. Ariëns, Nanne Bloksma, A.h. Penninks
    Abstract:

    Effects of the thymus atrophy-inducing Organotin Compound di-n-butyltin dichloride (DBTC) on the differentiation and proliferation of immature rat thymocyte subsets were studied in vivo and in vitro. Incubation of freshly isolated CD4-CD8- or immature CD4-CD8+ (characterized as CD4-CD53-) thymocytes with 10(-7) M DBTC for 18 hr did not affect cell recovery or their ability to differentiate to CD4-CD8+ cells and CD4+CD8+ or to CD4+CD8+ cells, respectively. The same treatment decreased the spontaneous as well as the phytohaemagglutinin (PHA)-induced proliferation in both subsets. However, the inhibition of proliferation by DBTC of immature CD4-CD8+, but not of CD4-CD8- thymocytes, appeared to increase with their growth rate. Data show that differentiation of immature thymocytes can proceed independently of proliferation and that DBTC causes thymus atrophy by selectively inhibiting the proliferation of immature CD4-CD8+ thymocytes. Administration to rats of DBTC via the diet for 14 days resulted in an initial decrease of thymoblast number by day 2, followed by a decrease in the total number of thymocytes by day 4. Total thymocyte numbers were lowest on day 7 and did not significantly change thereafter. CD4/CD8 thymocyte subset distributions were similar to controls on day 4, but on day 7 of feeding a marked reduction of the percentage of CD4+CD8+ thymocytes and consequently an increase of the percentages of the three other CD4/CD8 subsets were found. Thereafter, the CD4/CD8 subset distribution recovered, reaching near control values on day 14, despite the very low numbers of thymoblasts and of total thymocytes at that time. Data together indicate that DBTC reduces the production of CD4+CD8+ and mature single-positive thymocytes by selectively inhibiting immature CD4-CD8+ thymocyte proliferation but without affecting the differentiation capacity of these cells. This suggests that thymocyte proliferation and differentiation are separately regulated processes.

  • Recovery from chemically induced thymus atrophy starts with CD4- CD8- CD2high TcR alpha beta-/low thymocytes and results in an increased formation of CD4- CD8- TcR alpha beta high thymocytes.
    Immunology, 1993
    Co-Authors: Raymond Pieters, B. W. Lam, Marianne Bol, Willem Seinen, Nanne Bloksma, A.h. Penninks
    Abstract:

    Regeneration of the thymus was studied in rats that were treated with a single oral dose of the Organotin Compound di-n-butyltin dichloride (DBTC). After an initial maximum depletion of cortical BrdU+ thymocytes on day 2 after treatment, repopulation appeared to start on day 3 as indicated by an increased number of BrdU+ cells in the subcapsular region. On day 5, when thymocyte depletion was most pronounced, a relative increase of BrdU+ cells was observed all over the cortex. In comparison with controls, the thymoblast population on day 5 appeared to harbour increased numbers of CD4- CD8- and immature CD4- CD8+ CD53- thymoblasts, while the number of CD4+ CD8+ blasts had decreased. In comparison with day 3, however, the number of CD4+ CD8+ blasts had increased again. Results together have been interpreted as indicative for thymus regeneration starting from CD4- CD8- blasts which differentiate to immature CD4- CD8+ and then to CD4+ CD8+ blasts. Further characterization revealed that the majority of the CD4- CD8- and CD4- CD8+ CD53- blasts expressed high levels of CD2 and no or low levels of T-cell receptor (TcR) alpha beta. The high expression of CD2 on repopulating thymoblasts may be an additional indication of their activated state and for a role of interaction with the ligand LFA-3 on thymic epithelial cells during this phase of thymocyte differentiation. The number of CD4- CD8- TcR alpha beta high cells was increased on day 5 after dosing. The origin of this population and the possible implication of its development during thymus regeneration after chemically induced thymus atrophy are discussed.

  • The Organotin-induced thymus atrophy, characterized by depletion of CD4+ CD8+ thymocytes, is preceded by a reduction of the immature CD4- CD8+ TcR alpha beta-/low CD2high thymoblast subset.
    Immunology, 1992
    Co-Authors: Raymond Pieters, B. W. Lam, Marianne Bol, Willem Seinen, A.h. Penninks
    Abstract:

    Thymic changes in the rat induced by the thymus atrophy-inducing Organotin Compound di-n-butyltin dichloride (DBTC) were examined using FACS analyses. The number of CD4+CD8+ thymocytes was reduced by DBTC treatment from Day 2 onwards and reached minimum level on Days 4 and 5 after dosing. On these days the CD4-CD8- and both the CD4-CD8+ and CD4+CD8- subsets were not affected. On Day 2 we observed a reduced proportion of transferrin receptor (CD71)-positive CD4-OX44- cells, representing the cycling immature CD4-CD8+ cells, and of CD71+OX44- cells, representing the cycling CD4+CD8+ cells, but not of CD71+CD4-CD8- cells. When compared to controls, the FSChigh cell population of DBTC-treated rats contained less CD4-OX44- and OX44- cells, which were further characterized as CD2high and T-cell receptor (TcR)alpha beta- low. Moreover, fewer TcR alpha beta high cells were detected in the OX44- thymoblast subset of DBTC-treated rats. The number of CD4-CD8- thymoblasts appeared marginally decreased while the numbers of CD4+OX44+ cells, representing mature CD4+ cells, were not affected. These data indicate that DBTC causes a preferential initial depletion of immature CD4-CD8+CD2high TcR alpha beta-low thymoblasts. This initial event may result in a decreased formation of CD4+CD8+ thymoblasts and of small CD4+CD8+ thymocytes. These characteristics of the initially depleted subset indicate a specific anti-proliferative effect of DBTC and may give clues for the mechanism involved in the induction of thymus atrophy.

Marianne Bol - One of the best experts on this subject based on the ideXlab platform.

  • The thymus atrophy inducing Organotin Compound DBTC stimulates TCRalfabeta-CD3 signalling in immature rat thymocytes
    Biochemical and biophysical research communications, 1995
    Co-Authors: Raymond Pieters, Marianne Bol, Willem Seinen, P. Punt, J.m. Van Dijken, A.h. Penninks
    Abstract:

    In the present study, we show that the thymus atrophy inducing Compound DBTC stimulates the intracellular release, but not the influx, of Ca2+ elicited by cross-linking of the TcRαβ-CD3-complex on rat thymocytes and inhibits capping of TcRαβ. Similarities with the effects of cytochalasin B together with the finding that DBTC also inhibited capping of CD8, whereas cross-linking of CD8 did not cause a Ca2+-response, suggest that DBTC interferes with TcRαβ-CD3-signalling by selective interference with cytoskeletal functioning. The responding thymocytes were CD53- and FSC(low), thus possibly including the non proliferating counterpart of the presumed immature CD4-CD8+CD53- target cells of DBTC. The present effects may therefore relate to the mechanisms of Organotin-induced thymus atrophy.

  • Selective inhibition of immature CD4-CD8+ thymocyte proliferation, but not differentiation, by the thymus atrophy-inducing Compound di-n-butyltin dichloride.
    Immunology, 1994
    Co-Authors: Raymond Pieters, Marianne Bol, Willem Seinen, P. Punt, T. Ariëns, Nanne Bloksma, A.h. Penninks
    Abstract:

    Effects of the thymus atrophy-inducing Organotin Compound di-n-butyltin dichloride (DBTC) on the differentiation and proliferation of immature rat thymocyte subsets were studied in vivo and in vitro. Incubation of freshly isolated CD4-CD8- or immature CD4-CD8+ (characterized as CD4-CD53-) thymocytes with 10(-7) M DBTC for 18 hr did not affect cell recovery or their ability to differentiate to CD4-CD8+ cells and CD4+CD8+ or to CD4+CD8+ cells, respectively. The same treatment decreased the spontaneous as well as the phytohaemagglutinin (PHA)-induced proliferation in both subsets. However, the inhibition of proliferation by DBTC of immature CD4-CD8+, but not of CD4-CD8- thymocytes, appeared to increase with their growth rate. Data show that differentiation of immature thymocytes can proceed independently of proliferation and that DBTC causes thymus atrophy by selectively inhibiting the proliferation of immature CD4-CD8+ thymocytes. Administration to rats of DBTC via the diet for 14 days resulted in an initial decrease of thymoblast number by day 2, followed by a decrease in the total number of thymocytes by day 4. Total thymocyte numbers were lowest on day 7 and did not significantly change thereafter. CD4/CD8 thymocyte subset distributions were similar to controls on day 4, but on day 7 of feeding a marked reduction of the percentage of CD4+CD8+ thymocytes and consequently an increase of the percentages of the three other CD4/CD8 subsets were found. Thereafter, the CD4/CD8 subset distribution recovered, reaching near control values on day 14, despite the very low numbers of thymoblasts and of total thymocytes at that time. Data together indicate that DBTC reduces the production of CD4+CD8+ and mature single-positive thymocytes by selectively inhibiting immature CD4-CD8+ thymocyte proliferation but without affecting the differentiation capacity of these cells. This suggests that thymocyte proliferation and differentiation are separately regulated processes.

  • Recovery from chemically induced thymus atrophy starts with CD4- CD8- CD2high TcR alpha beta-/low thymocytes and results in an increased formation of CD4- CD8- TcR alpha beta high thymocytes.
    Immunology, 1993
    Co-Authors: Raymond Pieters, B. W. Lam, Marianne Bol, Willem Seinen, Nanne Bloksma, A.h. Penninks
    Abstract:

    Regeneration of the thymus was studied in rats that were treated with a single oral dose of the Organotin Compound di-n-butyltin dichloride (DBTC). After an initial maximum depletion of cortical BrdU+ thymocytes on day 2 after treatment, repopulation appeared to start on day 3 as indicated by an increased number of BrdU+ cells in the subcapsular region. On day 5, when thymocyte depletion was most pronounced, a relative increase of BrdU+ cells was observed all over the cortex. In comparison with controls, the thymoblast population on day 5 appeared to harbour increased numbers of CD4- CD8- and immature CD4- CD8+ CD53- thymoblasts, while the number of CD4+ CD8+ blasts had decreased. In comparison with day 3, however, the number of CD4+ CD8+ blasts had increased again. Results together have been interpreted as indicative for thymus regeneration starting from CD4- CD8- blasts which differentiate to immature CD4- CD8+ and then to CD4+ CD8+ blasts. Further characterization revealed that the majority of the CD4- CD8- and CD4- CD8+ CD53- blasts expressed high levels of CD2 and no or low levels of T-cell receptor (TcR) alpha beta. The high expression of CD2 on repopulating thymoblasts may be an additional indication of their activated state and for a role of interaction with the ligand LFA-3 on thymic epithelial cells during this phase of thymocyte differentiation. The number of CD4- CD8- TcR alpha beta high cells was increased on day 5 after dosing. The origin of this population and the possible implication of its development during thymus regeneration after chemically induced thymus atrophy are discussed.

  • The Organotin-induced thymus atrophy, characterized by depletion of CD4+ CD8+ thymocytes, is preceded by a reduction of the immature CD4- CD8+ TcR alpha beta-/low CD2high thymoblast subset.
    Immunology, 1992
    Co-Authors: Raymond Pieters, B. W. Lam, Marianne Bol, Willem Seinen, A.h. Penninks
    Abstract:

    Thymic changes in the rat induced by the thymus atrophy-inducing Organotin Compound di-n-butyltin dichloride (DBTC) were examined using FACS analyses. The number of CD4+CD8+ thymocytes was reduced by DBTC treatment from Day 2 onwards and reached minimum level on Days 4 and 5 after dosing. On these days the CD4-CD8- and both the CD4-CD8+ and CD4+CD8- subsets were not affected. On Day 2 we observed a reduced proportion of transferrin receptor (CD71)-positive CD4-OX44- cells, representing the cycling immature CD4-CD8+ cells, and of CD71+OX44- cells, representing the cycling CD4+CD8+ cells, but not of CD71+CD4-CD8- cells. When compared to controls, the FSChigh cell population of DBTC-treated rats contained less CD4-OX44- and OX44- cells, which were further characterized as CD2high and T-cell receptor (TcR)alpha beta- low. Moreover, fewer TcR alpha beta high cells were detected in the OX44- thymoblast subset of DBTC-treated rats. The number of CD4-CD8- thymoblasts appeared marginally decreased while the numbers of CD4+OX44+ cells, representing mature CD4+ cells, were not affected. These data indicate that DBTC causes a preferential initial depletion of immature CD4-CD8+CD2high TcR alpha beta-low thymoblasts. This initial event may result in a decreased formation of CD4+CD8+ thymoblasts and of small CD4+CD8+ thymocytes. These characteristics of the initially depleted subset indicate a specific anti-proliferative effect of DBTC and may give clues for the mechanism involved in the induction of thymus atrophy.

B. W. Lam - One of the best experts on this subject based on the ideXlab platform.

  • Recovery from chemically induced thymus atrophy starts with CD4- CD8- CD2high TcR alpha beta-/low thymocytes and results in an increased formation of CD4- CD8- TcR alpha beta high thymocytes.
    Immunology, 1993
    Co-Authors: Raymond Pieters, B. W. Lam, Marianne Bol, Willem Seinen, Nanne Bloksma, A.h. Penninks
    Abstract:

    Regeneration of the thymus was studied in rats that were treated with a single oral dose of the Organotin Compound di-n-butyltin dichloride (DBTC). After an initial maximum depletion of cortical BrdU+ thymocytes on day 2 after treatment, repopulation appeared to start on day 3 as indicated by an increased number of BrdU+ cells in the subcapsular region. On day 5, when thymocyte depletion was most pronounced, a relative increase of BrdU+ cells was observed all over the cortex. In comparison with controls, the thymoblast population on day 5 appeared to harbour increased numbers of CD4- CD8- and immature CD4- CD8+ CD53- thymoblasts, while the number of CD4+ CD8+ blasts had decreased. In comparison with day 3, however, the number of CD4+ CD8+ blasts had increased again. Results together have been interpreted as indicative for thymus regeneration starting from CD4- CD8- blasts which differentiate to immature CD4- CD8+ and then to CD4+ CD8+ blasts. Further characterization revealed that the majority of the CD4- CD8- and CD4- CD8+ CD53- blasts expressed high levels of CD2 and no or low levels of T-cell receptor (TcR) alpha beta. The high expression of CD2 on repopulating thymoblasts may be an additional indication of their activated state and for a role of interaction with the ligand LFA-3 on thymic epithelial cells during this phase of thymocyte differentiation. The number of CD4- CD8- TcR alpha beta high cells was increased on day 5 after dosing. The origin of this population and the possible implication of its development during thymus regeneration after chemically induced thymus atrophy are discussed.

  • The Organotin-induced thymus atrophy, characterized by depletion of CD4+ CD8+ thymocytes, is preceded by a reduction of the immature CD4- CD8+ TcR alpha beta-/low CD2high thymoblast subset.
    Immunology, 1992
    Co-Authors: Raymond Pieters, B. W. Lam, Marianne Bol, Willem Seinen, A.h. Penninks
    Abstract:

    Thymic changes in the rat induced by the thymus atrophy-inducing Organotin Compound di-n-butyltin dichloride (DBTC) were examined using FACS analyses. The number of CD4+CD8+ thymocytes was reduced by DBTC treatment from Day 2 onwards and reached minimum level on Days 4 and 5 after dosing. On these days the CD4-CD8- and both the CD4-CD8+ and CD4+CD8- subsets were not affected. On Day 2 we observed a reduced proportion of transferrin receptor (CD71)-positive CD4-OX44- cells, representing the cycling immature CD4-CD8+ cells, and of CD71+OX44- cells, representing the cycling CD4+CD8+ cells, but not of CD71+CD4-CD8- cells. When compared to controls, the FSChigh cell population of DBTC-treated rats contained less CD4-OX44- and OX44- cells, which were further characterized as CD2high and T-cell receptor (TcR)alpha beta- low. Moreover, fewer TcR alpha beta high cells were detected in the OX44- thymoblast subset of DBTC-treated rats. The number of CD4-CD8- thymoblasts appeared marginally decreased while the numbers of CD4+OX44+ cells, representing mature CD4+ cells, were not affected. These data indicate that DBTC causes a preferential initial depletion of immature CD4-CD8+CD2high TcR alpha beta-low thymoblasts. This initial event may result in a decreased formation of CD4+CD8+ thymoblasts and of small CD4+CD8+ thymocytes. These characteristics of the initially depleted subset indicate a specific anti-proliferative effect of DBTC and may give clues for the mechanism involved in the induction of thymus atrophy.