The Experts below are selected from a list of 204999 Experts worldwide ranked by ideXlab platform
Robyn E Ohehir - One of the best experts on this subject based on the ideXlab platform.
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the effects of changes at peptide residues contacting mhc class ii t Cell receptor on antigen recognition and human Th0 Cell effector function
Immunology, 1995Co-Authors: J R Lamb, J A Higgins, Charlotte Hetzel, John D Hayball, Richard A Lake, Robyn E OhehirAbstract:Cytokines can influence the selection of functional subsets (Th1 or Th2) of CD4+ T Cells. However, quantitative changes in affinity of peptide/major histocompatibility complex (MHC) class II/T-Cell receptor (TCR) interactions may alter antigen density and modulate T-Cell effector function. The possibility exists to use peptide analogues to induce a partial signal to dissociate production of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) by T-helper type-0 (Th0) Cells and, consequently, to regulate T-Cell function. Based on binding assays and resolution of the crystalline structure of an influenza virus haemagglutinin peptide (HA 306-318) bound to the human MHC class II molecule DRB1*0101, we synthesized HA peptide analogues with amino acid substitutions predicted to modify either MHC class II/peptide density or TCR/peptide interactions. When we examined their antigenicity using cloned human Th0 Cells, the analogues, in general, elicited a gradation in potency reflected by a reduction in both proliferation and cytokine production (IL-2, IL-4 and IFN-gamma). Although the analogue HA-R309 diminished IL-2 production, none of the analogues tested could selectively induce only IL-4 or IFN-gamma. Since, in general, the effector functions of the Th0 Cells examined here were resistant to selective manipulation by the peptide analogues, this suggests that for some clones of chronically activated T Cells modulation of selected functions may be difficult to achieve.
Lucette Pelletier - One of the best experts on this subject based on the ideXlab platform.
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self reactive anti class ii t helper type 2 Cell lines derived from gold salt injected rats trigger b Cell polyclonal activation and transfer autoimmunity in cd8 depleted normal syngeneic recipients
European Journal of Immunology, 1995Co-Authors: Abdelhadi Saoudi, Maria Castedo, Dominique Nochy, Chantal Mandet, Regine Pasquier, Philippe Druet, Lucette PelletierAbstract:: Brown Norway (BN) rats given gold salts develop an autoimmune syndrome with an immune complex-type glomerulonephritis in the context of a polyclonal B Cell activation that was suspected to be due to the emergence of anti-self major histocompatibility complex (MHC) class II T Cells. In the present study, six anti-self MHC class II T Cell lines have been derived from six gold salt-treated rats by repeated stimulations with normal syngeneic MHC class II-bearing Cells. The T Cell lines proliferated in the presence of self MHC class II-positive B Cell-enriched or B Cell-depleted Cells and the proliferation was inhibited by preincubating stimulator Cells with an anti-IA monoclonal antibody. The T Cell lines produced interleukin (IL)-4 only or IL-4 and some interferon (IFN)-gamma and could, therefore, be considered as T helper type 2 (Th2) and Th0 Cells, respectively. They triggered normal syngeneic B Cells to produce in vitro IgE, anti-DNA, anti-laminin and anti-2,4-6-trinitrophenol antibodies through, at least in part, cognate interactions. More interestingly, these lines when transferred into normal BN rats induced an autoimmune syndrome similar to or even more severe than the one observed in the active gold model, provided the recipients were CD8 depleted. These manifestations included a dramatic increase in serum IgE concentration and the production of anti-DNA and anti-laminin antibodies. In addition, all recipients displayed an autoimmune glomerulonephritis due to anti-laminin antibodies, granular IgG deposits in the interstitium, in the vessel walls and along the tubular basement membranes and a severe tubulointerstitial nephritis with marked mononuclear Cell infiltration. An anti-ovalbumin T Cell line that produced IL-4 and low amounts of IFN-gamma was used as a control and did not induce autoimmunity. These results demonstrate for the first time the ability of autoreactive Th2 as well as Th0 Cell lines to induce antibody-mediated autoimmunity. They also show that CD8+ Cells play a crucial role in the control of such autoreactive Cells. Finally, this work suggests that Th2 Cells could initiate Cell-mediated reactions either directly or indirectly.
J R Lamb - One of the best experts on this subject based on the ideXlab platform.
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the effects of changes at peptide residues contacting mhc class ii t Cell receptor on antigen recognition and human Th0 Cell effector function
Immunology, 1995Co-Authors: J R Lamb, J A Higgins, Charlotte Hetzel, John D Hayball, Richard A Lake, Robyn E OhehirAbstract:Cytokines can influence the selection of functional subsets (Th1 or Th2) of CD4+ T Cells. However, quantitative changes in affinity of peptide/major histocompatibility complex (MHC) class II/T-Cell receptor (TCR) interactions may alter antigen density and modulate T-Cell effector function. The possibility exists to use peptide analogues to induce a partial signal to dissociate production of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) by T-helper type-0 (Th0) Cells and, consequently, to regulate T-Cell function. Based on binding assays and resolution of the crystalline structure of an influenza virus haemagglutinin peptide (HA 306-318) bound to the human MHC class II molecule DRB1*0101, we synthesized HA peptide analogues with amino acid substitutions predicted to modify either MHC class II/peptide density or TCR/peptide interactions. When we examined their antigenicity using cloned human Th0 Cells, the analogues, in general, elicited a gradation in potency reflected by a reduction in both proliferation and cytokine production (IL-2, IL-4 and IFN-gamma). Although the analogue HA-R309 diminished IL-2 production, none of the analogues tested could selectively induce only IL-4 or IFN-gamma. Since, in general, the effector functions of the Th0 Cells examined here were resistant to selective manipulation by the peptide analogues, this suggests that for some clones of chronically activated T Cells modulation of selected functions may be difficult to achieve.
Abdelhadi Saoudi - One of the best experts on this subject based on the ideXlab platform.
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self reactive anti class ii t helper type 2 Cell lines derived from gold salt injected rats trigger b Cell polyclonal activation and transfer autoimmunity in cd8 depleted normal syngeneic recipients
European Journal of Immunology, 1995Co-Authors: Abdelhadi Saoudi, Maria Castedo, Dominique Nochy, Chantal Mandet, Regine Pasquier, Philippe Druet, Lucette PelletierAbstract:: Brown Norway (BN) rats given gold salts develop an autoimmune syndrome with an immune complex-type glomerulonephritis in the context of a polyclonal B Cell activation that was suspected to be due to the emergence of anti-self major histocompatibility complex (MHC) class II T Cells. In the present study, six anti-self MHC class II T Cell lines have been derived from six gold salt-treated rats by repeated stimulations with normal syngeneic MHC class II-bearing Cells. The T Cell lines proliferated in the presence of self MHC class II-positive B Cell-enriched or B Cell-depleted Cells and the proliferation was inhibited by preincubating stimulator Cells with an anti-IA monoclonal antibody. The T Cell lines produced interleukin (IL)-4 only or IL-4 and some interferon (IFN)-gamma and could, therefore, be considered as T helper type 2 (Th2) and Th0 Cells, respectively. They triggered normal syngeneic B Cells to produce in vitro IgE, anti-DNA, anti-laminin and anti-2,4-6-trinitrophenol antibodies through, at least in part, cognate interactions. More interestingly, these lines when transferred into normal BN rats induced an autoimmune syndrome similar to or even more severe than the one observed in the active gold model, provided the recipients were CD8 depleted. These manifestations included a dramatic increase in serum IgE concentration and the production of anti-DNA and anti-laminin antibodies. In addition, all recipients displayed an autoimmune glomerulonephritis due to anti-laminin antibodies, granular IgG deposits in the interstitium, in the vessel walls and along the tubular basement membranes and a severe tubulointerstitial nephritis with marked mononuclear Cell infiltration. An anti-ovalbumin T Cell line that produced IL-4 and low amounts of IFN-gamma was used as a control and did not induce autoimmunity. These results demonstrate for the first time the ability of autoreactive Th2 as well as Th0 Cell lines to induce antibody-mediated autoimmunity. They also show that CD8+ Cells play a crucial role in the control of such autoreactive Cells. Finally, this work suggests that Th2 Cells could initiate Cell-mediated reactions either directly or indirectly.
Richard A Lake - One of the best experts on this subject based on the ideXlab platform.
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the effects of changes at peptide residues contacting mhc class ii t Cell receptor on antigen recognition and human Th0 Cell effector function
Immunology, 1995Co-Authors: J R Lamb, J A Higgins, Charlotte Hetzel, John D Hayball, Richard A Lake, Robyn E OhehirAbstract:Cytokines can influence the selection of functional subsets (Th1 or Th2) of CD4+ T Cells. However, quantitative changes in affinity of peptide/major histocompatibility complex (MHC) class II/T-Cell receptor (TCR) interactions may alter antigen density and modulate T-Cell effector function. The possibility exists to use peptide analogues to induce a partial signal to dissociate production of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) by T-helper type-0 (Th0) Cells and, consequently, to regulate T-Cell function. Based on binding assays and resolution of the crystalline structure of an influenza virus haemagglutinin peptide (HA 306-318) bound to the human MHC class II molecule DRB1*0101, we synthesized HA peptide analogues with amino acid substitutions predicted to modify either MHC class II/peptide density or TCR/peptide interactions. When we examined their antigenicity using cloned human Th0 Cells, the analogues, in general, elicited a gradation in potency reflected by a reduction in both proliferation and cytokine production (IL-2, IL-4 and IFN-gamma). Although the analogue HA-R309 diminished IL-2 production, none of the analogues tested could selectively induce only IL-4 or IFN-gamma. Since, in general, the effector functions of the Th0 Cells examined here were resistant to selective manipulation by the peptide analogues, this suggests that for some clones of chronically activated T Cells modulation of selected functions may be difficult to achieve.