The Experts below are selected from a list of 75000 Experts worldwide ranked by ideXlab platform
Xun Sun - One of the best experts on this subject based on the ideXlab platform.
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CD30 Ligand deficiency accelerates glioma progression by promoting the formation of tumor immune microenvironment
International Immunopharmacology, 2019Co-Authors: Jin Duan, Yasunobu Yoshikai, Yaxian Gao, Xiaoqing Zhang, Xiao Wang, Biao Wang, Xin Meng, Yuanyuan Wang, Xun SunAbstract:CD30 Ligand (CD30L, CD153), belonging to the tumor necrosis factor superfamily, has been reported to act as an immune regulator mainly in several autoimmune diseases and Hodgkin's lymphoma. However, little is known about its regulation in the glioma microenvironment. In this study, using a GL261 mouse glioma model, we showed that CD30L deficiency in the host accelerated glioma growth and reduced mouse survival, which might be associated with the accumulation of tumor-infiltrating immune cells, especially tumor-associated macrophages, myeloid-derived suppressor cells and CD8+ PD-1+ T cells. Moreover, CD30L deficiency resulted in distinct subsets of tumor-associated macrophages compared with those of wild-type mice. Furthermore, compared with those of wild-type mice, tumor-associated macrophages and microglia in CD30L-deficient mice adopted a more pro-tumorigenic phenotype within tumors. CD8+ T cells in CD30L-deficient mice decreased the expression of ki-67. Therefore, these results suggest that CD30L deficiency promotes the exhaustion of CD8+ T cells and the infiltration of tumor-associated macrophages and microglia. Our findings provide evidence for a new potential immunotherapy for glioma targeting CD30/CD30L signaling.
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CD30 Ligand is a new therapeutic target for central nervous system autoimmunity
Journal of Autoimmunity, 2015Co-Authors: Koji Shinoda, Hiromi Muta, Xun Sun, Eckhard R Podack, Akiko Oyamada, Hisakata Yamada, Jun Ichi Kira, Yasunobu YoshikaiAbstract:The CD30 Ligand (CD30L)/CD30 axis plays a critical role in Th1 and Th17 cell differentiation. However, the role in the pathogenesis of central nervous system autoimmunity remains unknown. Here we show the resistance for experimental autoimmune encephalomyelitis (EAE) with markedly reduced induction of antigen-specific Th1 and Th17 cells in CD30L knockout mice. Bone marrow chimera experiments indicated that CD30L on bone marrow-derived cells were critical for the development of EAE and that CD30L reverse signaling in CD4 T cells was dispensable for the pathogenic Th17 cell differentiation at the induction phase. Adoptive transfer experiment revealed an additional role for CD30L in the environment at the effector phase. In vivo neutralization of CD30L by soluble murine CD30-Immunoglobulin fusion protein before disease onset or even after disease onset significantly ameliorated the clinical symptoms. These results indicate that CD30L/CD30 signaling is critically involved in antigen-specific CD4 T cell responses at both the induction and effector phase, thus could be a new target molecule for the treatment of central nervous system autoimmunity.
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CD30 Ligand CD30 interaction is involved in pathogenesis of inflammatory bowel disease
Digestive Diseases and Sciences, 2012Co-Authors: Shinichi Somada, Hiromi Muta, Kazuhiko Nakamura, Xun Sun, Kuniomi Honda, Eikichi Ihara, Hirotada Akiho, Ryoichi Takayanagi, Yasunobu YoshikaiAbstract:Background and Aims Although CD30 has long been recognized as an important marker in many lymphomas of diverse origin, and as an activation molecule on B and T cells, its primary function has remained obscure. Soluble CD30 (sCD30) is released from CD30 on the cell membrane by enzymatic cleavage. This study investigated the role of CD30 Ligand (CD30L)/CD30 signals in intestinal mucosal damage.
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CD30 Ligand is a target for a novel biological therapy against colitis associated with th17 responses
Journal of Immunology, 2010Co-Authors: Xun Sun, Hiromi Muta, Eckhard R Podack, Kenzaburo Tani, Hisakata Yamada, Kensuke Shibata, Yoichiro Iwakura, Yasunobu YoshikaiAbstract:We have previously found that CD30 Ligand (CD30L; CD153)/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production. In this study, we investigated the role of CD30L in the development of colitis experimentally induced by dextran sulfate sodium (DSS), in which IL-17A is involved in the pathogenesis. CD30L(-/-) mice were resistant to both acute colitis induced by administration of 3 to ∼ 5% DSS and to chronic colitis induced by administration of 1.5% DSS on days 0-5, 10-15, and 20-25 as assessed by weight loss, survival rate, and histopathology. The levels of IFN-γ, IL-17A, and IL-10 were significantly lower but the IL-2 level higher in the lamina propria T lymphocytes of CD30L(-/-) mice than those in lamina propria T lymphocytes of wild-type mice after DSS administration. Soluble murine CD30-Ig fusion protein, which was capable of inhibiting Th17 cell differentiation in vitro, ameliorated both types of DSS-induced colitis in wild-type mice. Modulation of CD30L/CD30 signaling by soluble CD30 could be a novel biological therapy for inflammatory diseases associated with Th17 responses.
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CD30 Ligand CD30 plays a critical role in th17 differentiation in mice
Journal of Immunology, 2010Co-Authors: Hiromi Muta, Xun Sun, Eckhard R Podack, Kenzaburo Tani, Hisakata Yamada, Kensuke Shibata, Yasunobu YoshikaiAbstract:A CD30 Ligand (CD30L; CD153) and its receptor, CD30, is a membrane-associated glycoprotein belonging to the TNF superfamily and TNFR superfamily. These were expressed preferentially by activated CD4(+)T cells. In this paper, we show that CD44(low)CD62(hi)CD4(+) T cells from CD30L(-/-) or CD30(-/-) mice exhibited impaired differentiation into Th17 cells but an increased ability to produce IL-2 after in vitro culture under Th17-polarizing conditions. Neutralization with IL-2 by anti-IL-2 mAb partly restored the ability of Th17 differentiation in CD30L(-/-) or CD30(-/-) T cells. Stimulation via CD30L by immobilized anti-CD30L mAb suppressed IL-2 production by CD30(-/-)CD4(+) T cells, indicating that the reverse signal to CD30L is responsible for downregulation of IL-2 production. In vivo Th17 differentiation of CD30L(-/-)CD4(+)CD45RB(high) T cells was also impaired after transfer into SCID mice, whereas CD30L(+/+)CD4(+)CD45RB(high) T cells normally differentiated into Th17 cells in CD30L(-/-) SCID mice. The results of these studies demonstrate that CD30L/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production.
Yasunobu Yoshikai - One of the best experts on this subject based on the ideXlab platform.
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CD30 Ligand deficiency accelerates glioma progression by promoting the formation of tumor immune microenvironment
International Immunopharmacology, 2019Co-Authors: Jin Duan, Yasunobu Yoshikai, Yaxian Gao, Xiaoqing Zhang, Xiao Wang, Biao Wang, Xin Meng, Yuanyuan Wang, Xun SunAbstract:CD30 Ligand (CD30L, CD153), belonging to the tumor necrosis factor superfamily, has been reported to act as an immune regulator mainly in several autoimmune diseases and Hodgkin's lymphoma. However, little is known about its regulation in the glioma microenvironment. In this study, using a GL261 mouse glioma model, we showed that CD30L deficiency in the host accelerated glioma growth and reduced mouse survival, which might be associated with the accumulation of tumor-infiltrating immune cells, especially tumor-associated macrophages, myeloid-derived suppressor cells and CD8+ PD-1+ T cells. Moreover, CD30L deficiency resulted in distinct subsets of tumor-associated macrophages compared with those of wild-type mice. Furthermore, compared with those of wild-type mice, tumor-associated macrophages and microglia in CD30L-deficient mice adopted a more pro-tumorigenic phenotype within tumors. CD8+ T cells in CD30L-deficient mice decreased the expression of ki-67. Therefore, these results suggest that CD30L deficiency promotes the exhaustion of CD8+ T cells and the infiltration of tumor-associated macrophages and microglia. Our findings provide evidence for a new potential immunotherapy for glioma targeting CD30/CD30L signaling.
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CD30 Ligand is a new therapeutic target for central nervous system autoimmunity
Journal of Autoimmunity, 2015Co-Authors: Koji Shinoda, Hiromi Muta, Xun Sun, Eckhard R Podack, Akiko Oyamada, Hisakata Yamada, Jun Ichi Kira, Yasunobu YoshikaiAbstract:The CD30 Ligand (CD30L)/CD30 axis plays a critical role in Th1 and Th17 cell differentiation. However, the role in the pathogenesis of central nervous system autoimmunity remains unknown. Here we show the resistance for experimental autoimmune encephalomyelitis (EAE) with markedly reduced induction of antigen-specific Th1 and Th17 cells in CD30L knockout mice. Bone marrow chimera experiments indicated that CD30L on bone marrow-derived cells were critical for the development of EAE and that CD30L reverse signaling in CD4 T cells was dispensable for the pathogenic Th17 cell differentiation at the induction phase. Adoptive transfer experiment revealed an additional role for CD30L in the environment at the effector phase. In vivo neutralization of CD30L by soluble murine CD30-Immunoglobulin fusion protein before disease onset or even after disease onset significantly ameliorated the clinical symptoms. These results indicate that CD30L/CD30 signaling is critically involved in antigen-specific CD4 T cell responses at both the induction and effector phase, thus could be a new target molecule for the treatment of central nervous system autoimmunity.
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CD30 Ligand CD30 interaction is involved in pathogenesis of inflammatory bowel disease
Digestive Diseases and Sciences, 2012Co-Authors: Shinichi Somada, Hiromi Muta, Kazuhiko Nakamura, Xun Sun, Kuniomi Honda, Eikichi Ihara, Hirotada Akiho, Ryoichi Takayanagi, Yasunobu YoshikaiAbstract:Background and Aims Although CD30 has long been recognized as an important marker in many lymphomas of diverse origin, and as an activation molecule on B and T cells, its primary function has remained obscure. Soluble CD30 (sCD30) is released from CD30 on the cell membrane by enzymatic cleavage. This study investigated the role of CD30 Ligand (CD30L)/CD30 signals in intestinal mucosal damage.
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CD30 Ligand is a target for a novel biological therapy against colitis associated with th17 responses
Journal of Immunology, 2010Co-Authors: Xun Sun, Hiromi Muta, Eckhard R Podack, Kenzaburo Tani, Hisakata Yamada, Kensuke Shibata, Yoichiro Iwakura, Yasunobu YoshikaiAbstract:We have previously found that CD30 Ligand (CD30L; CD153)/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production. In this study, we investigated the role of CD30L in the development of colitis experimentally induced by dextran sulfate sodium (DSS), in which IL-17A is involved in the pathogenesis. CD30L(-/-) mice were resistant to both acute colitis induced by administration of 3 to ∼ 5% DSS and to chronic colitis induced by administration of 1.5% DSS on days 0-5, 10-15, and 20-25 as assessed by weight loss, survival rate, and histopathology. The levels of IFN-γ, IL-17A, and IL-10 were significantly lower but the IL-2 level higher in the lamina propria T lymphocytes of CD30L(-/-) mice than those in lamina propria T lymphocytes of wild-type mice after DSS administration. Soluble murine CD30-Ig fusion protein, which was capable of inhibiting Th17 cell differentiation in vitro, ameliorated both types of DSS-induced colitis in wild-type mice. Modulation of CD30L/CD30 signaling by soluble CD30 could be a novel biological therapy for inflammatory diseases associated with Th17 responses.
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CD30 Ligand CD30 plays a critical role in th17 differentiation in mice
Journal of Immunology, 2010Co-Authors: Hiromi Muta, Xun Sun, Eckhard R Podack, Kenzaburo Tani, Hisakata Yamada, Kensuke Shibata, Yasunobu YoshikaiAbstract:A CD30 Ligand (CD30L; CD153) and its receptor, CD30, is a membrane-associated glycoprotein belonging to the TNF superfamily and TNFR superfamily. These were expressed preferentially by activated CD4(+)T cells. In this paper, we show that CD44(low)CD62(hi)CD4(+) T cells from CD30L(-/-) or CD30(-/-) mice exhibited impaired differentiation into Th17 cells but an increased ability to produce IL-2 after in vitro culture under Th17-polarizing conditions. Neutralization with IL-2 by anti-IL-2 mAb partly restored the ability of Th17 differentiation in CD30L(-/-) or CD30(-/-) T cells. Stimulation via CD30L by immobilized anti-CD30L mAb suppressed IL-2 production by CD30(-/-)CD4(+) T cells, indicating that the reverse signal to CD30L is responsible for downregulation of IL-2 production. In vivo Th17 differentiation of CD30L(-/-)CD4(+)CD45RB(high) T cells was also impaired after transfer into SCID mice, whereas CD30L(+/+)CD4(+)CD45RB(high) T cells normally differentiated into Th17 cells in CD30L(-/-) SCID mice. The results of these studies demonstrate that CD30L/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production.
Hiromi Muta - One of the best experts on this subject based on the ideXlab platform.
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CD30 Ligand is a new therapeutic target for central nervous system autoimmunity
Journal of Autoimmunity, 2015Co-Authors: Koji Shinoda, Hiromi Muta, Xun Sun, Eckhard R Podack, Akiko Oyamada, Hisakata Yamada, Jun Ichi Kira, Yasunobu YoshikaiAbstract:The CD30 Ligand (CD30L)/CD30 axis plays a critical role in Th1 and Th17 cell differentiation. However, the role in the pathogenesis of central nervous system autoimmunity remains unknown. Here we show the resistance for experimental autoimmune encephalomyelitis (EAE) with markedly reduced induction of antigen-specific Th1 and Th17 cells in CD30L knockout mice. Bone marrow chimera experiments indicated that CD30L on bone marrow-derived cells were critical for the development of EAE and that CD30L reverse signaling in CD4 T cells was dispensable for the pathogenic Th17 cell differentiation at the induction phase. Adoptive transfer experiment revealed an additional role for CD30L in the environment at the effector phase. In vivo neutralization of CD30L by soluble murine CD30-Immunoglobulin fusion protein before disease onset or even after disease onset significantly ameliorated the clinical symptoms. These results indicate that CD30L/CD30 signaling is critically involved in antigen-specific CD4 T cell responses at both the induction and effector phase, thus could be a new target molecule for the treatment of central nervous system autoimmunity.
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CD30 Ligand CD30 interaction is involved in pathogenesis of inflammatory bowel disease
Digestive Diseases and Sciences, 2012Co-Authors: Shinichi Somada, Hiromi Muta, Kazuhiko Nakamura, Xun Sun, Kuniomi Honda, Eikichi Ihara, Hirotada Akiho, Ryoichi Takayanagi, Yasunobu YoshikaiAbstract:Background and Aims Although CD30 has long been recognized as an important marker in many lymphomas of diverse origin, and as an activation molecule on B and T cells, its primary function has remained obscure. Soluble CD30 (sCD30) is released from CD30 on the cell membrane by enzymatic cleavage. This study investigated the role of CD30 Ligand (CD30L)/CD30 signals in intestinal mucosal damage.
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CD30 Ligand is a target for a novel biological therapy against colitis associated with th17 responses
Journal of Immunology, 2010Co-Authors: Xun Sun, Hiromi Muta, Eckhard R Podack, Kenzaburo Tani, Hisakata Yamada, Kensuke Shibata, Yoichiro Iwakura, Yasunobu YoshikaiAbstract:We have previously found that CD30 Ligand (CD30L; CD153)/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production. In this study, we investigated the role of CD30L in the development of colitis experimentally induced by dextran sulfate sodium (DSS), in which IL-17A is involved in the pathogenesis. CD30L(-/-) mice were resistant to both acute colitis induced by administration of 3 to ∼ 5% DSS and to chronic colitis induced by administration of 1.5% DSS on days 0-5, 10-15, and 20-25 as assessed by weight loss, survival rate, and histopathology. The levels of IFN-γ, IL-17A, and IL-10 were significantly lower but the IL-2 level higher in the lamina propria T lymphocytes of CD30L(-/-) mice than those in lamina propria T lymphocytes of wild-type mice after DSS administration. Soluble murine CD30-Ig fusion protein, which was capable of inhibiting Th17 cell differentiation in vitro, ameliorated both types of DSS-induced colitis in wild-type mice. Modulation of CD30L/CD30 signaling by soluble CD30 could be a novel biological therapy for inflammatory diseases associated with Th17 responses.
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CD30 Ligand CD30 plays a critical role in th17 differentiation in mice
Journal of Immunology, 2010Co-Authors: Hiromi Muta, Xun Sun, Eckhard R Podack, Kenzaburo Tani, Hisakata Yamada, Kensuke Shibata, Yasunobu YoshikaiAbstract:A CD30 Ligand (CD30L; CD153) and its receptor, CD30, is a membrane-associated glycoprotein belonging to the TNF superfamily and TNFR superfamily. These were expressed preferentially by activated CD4(+)T cells. In this paper, we show that CD44(low)CD62(hi)CD4(+) T cells from CD30L(-/-) or CD30(-/-) mice exhibited impaired differentiation into Th17 cells but an increased ability to produce IL-2 after in vitro culture under Th17-polarizing conditions. Neutralization with IL-2 by anti-IL-2 mAb partly restored the ability of Th17 differentiation in CD30L(-/-) or CD30(-/-) T cells. Stimulation via CD30L by immobilized anti-CD30L mAb suppressed IL-2 production by CD30(-/-)CD4(+) T cells, indicating that the reverse signal to CD30L is responsible for downregulation of IL-2 production. In vivo Th17 differentiation of CD30L(-/-)CD4(+)CD45RB(high) T cells was also impaired after transfer into SCID mice, whereas CD30L(+/+)CD4(+)CD45RB(high) T cells normally differentiated into Th17 cells in CD30L(-/-) SCID mice. The results of these studies demonstrate that CD30L/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production.
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a critical role of CD30 Ligand CD30 in controlling inflammatory bowel diseases in mice
Gastroenterology, 2008Co-Authors: Xun Sun, Shinichi Somada, Hiromi Muta, Kazuhiko Nakamura, Kuniomi Honda, Hisakata Yamada, Kensuke Shibata, Hirofumi Yoshihara, Ryhoichi Takayanagi, Kenzaburo TaniAbstract:Background & Aims: A CD30-Ligand (CD30L) is a 40-kilodalton, type II membrane-associated glycoprotein belonging to the tumor necrosis factor family. Serum levels of soluble CD30 increased in inflammatory bowel diseases (IBD), suggesting that CD30L/CD30 signaling is involved in the pathogenesis of IBD. In this study, we investigated the role of CD30L in oxazolone (OXA)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis in CD30L knockout (KO) mice. Methods: Colitis was induced by OXA or TNBS in CD30LKO mice with BALB/c or C57BL/6 background, respectively, and diverse clinical signs of the disease were evaluated. Cytokine production from lamina propria T cells of the colon was assessed by enzyme-linked immunosorbent assay. Anti-interleukin (IL)-4 monoclonal antibody (mAb) or agonistic anti-CD30 mAb was inoculated in mice with colitis induced by OXA or TNBS. Results: CD30LKO mice were susceptible to OXA-induced colitis but resistant to TNBS-induced acute colitis. The levels of T helper cell 2 type cytokines such as IL-4 and IL-13 in the LP T cells were significantly higher, but the levels of interferon γ were lower in OXA- or TNBS-treated CD30LKO mice than in wild-type mice. In vivo administration of agonistic anti-CD30 mAb ameliorated OXA-induced colitis but aggravated TNBS-induced colitis in CD30LKO mice. Conclusions: These results suggest that CD30L/CD30 signaling is involved in development of both OXA- and TNBS-induced colitis. Modulation of CD30L/CD30 signaling by mAb could be a novel biologic therapy for IBD.
Craig A. Smith - One of the best experts on this subject based on the ideXlab platform.
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Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: A soluble, secreted CD30 homologue
Proceedings of the National Academy of Sciences of the United States of America, 2002Co-Authors: Joanne Fanelli Panus, Craig A. Smith, Dhavalkumar D. Patel, Caroline A. Ray, Terri Davis Smith, David J. PickupAbstract:Cowpox virus (Brighton Red strain) possesses one of the largest genomes in the Orthopoxvirus genus. Sequence analysis of a region of the genome that is type-specific for cowpox virus identified a gene, vCD30, encoding a soluble, secreted protein that is the fifth member of the tumor necrosis factor receptor family known to be encoded by cowpox virus. The vCD30 protein contains 110 aa, including a 21-residue signal peptide, a potential O-linked glycosylation site, and a 58-aa sequence sharing 51-59% identity with highly conserved extracellular segments of both mouse and human CD30. A vCD30Fc fusion protein binds CD153 (CD30 Ligand) specifically, and it completely inhibits CD153/CD30 interactions. Although the functions of CD30 are not well understood, the existence of vCD30 suggests that the cellular receptor plays a significant role in normal immune responses. Viral inhibition of CD30 also lends support to the potential therapeutic value of targeting CD30 in human inflammatory and autoimmune diseases.
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reverse signaling via CD30 Ligand
Journal of Immunology, 1996Co-Authors: Steven R Wiley, Raymond G. Goodwin, Craig A. SmithAbstract:CD30 Ligand (CD30L), a member of the TNF family, is a type II membrane protein with a C-terminal extracellular domain that is homologous with the extracellular domains of other TNF family members. Also, like most TNF family members, the N-terminal cytoplasmic domain of CD30L is conserved across species, but not between family members, suggesting a possible biological function. Motivated by this observation, we investigated the potential for CD30L, when activated by cross-linking, to directly transduce a signal to the Ligand-bearing cell. Cross-linking of CD30L by a mAb or by CD30-Fc fusion protein induced the production of IL-8 by freshly isolated neutrophils. Further, both cross-linking mechanisms produced a rapid oxidative burst. Indirect effects through CD30 were ruled out, since CD30L, but not CD30, is expressed on neutrophils. Expression of CD30L can be induced in peripheral blood T cells by cross-linking the CD3 component of the TCR. Peripheral blood T cells exposed to suboptimal concentrations of anti-CD3 increased metabolic activity, proliferated, and produced IL-6 in response to cross-linking of CD30L. These results indicate that cross-linked CD30L can transduce a signal to the Ligand-bearing cell. This "reverse signaling" via CD30L taken together with previously published data concerning other Ligands in the TNF family strongly suggest that, as a rule, TNF family members and their cognate receptors signal bidirectionally, blurring the distinction between Ligand and receptor.
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CD30 Ligand expression in nonmalignant and hodgkin s disease involved lymphoid tissues
American Journal of Pathology, 1996Co-Authors: H J Gruss, Norman Boiani, A Pinto, Annunziata Gloghini, E Wehnes, B Wright, Donatella Aldinucci, Valter Gattei, Vittorina Zagonel, Craig A. SmithAbstract:The CD30 Ligand (CD30L) is a type II transmembrane glycoprotein of the tumor necrosis factor Ligand superfamily. Recent cloning of CD30L has enabled studies to explore its function and tissue distribution. For instance, recombinant CD30L has been shown to co-stimulate T cells and to act as mitogen for Hodgkin's disease (HD)-derived cell lines. The counter-receptor for CD30L, ie, CD30, is a type I cytokine receptor that is highly expressed by activated T cells, Hodgkin and Reed-Sternberg (H-RS) cells, and anaplastic large cell lymphoma cells. In the present study, recombinant membrane-bound and soluble human CD30L were instrumental to raise a monoclonal antibody (M80) recognizing membrane-bound CD30L on transfected and native cells. With this reagent, a panel of cultured lymphoma-derived cell lines as well as primary normal, reactive, and HD-involved lymphoid tissues were examined for expression of CD30L by immunostaining and flow cytometry. In reactive lymphnodes and tonsils, CD30L was expressed by a small subset of lymphoid cells, histiocytes, and granulocytes. Higher levels of CD30L expression were noted in HD lesions among bystander cells; ie, T cells and granulocytes that surrounded H-RS cells. Native CD30L displayed at the cell surface was functionally active as shown by the ability of fixed granulocytes to interact with CD30+ cell lines. Moreover, CD30L was detectable, although to a lower staining intensity, in primary H-RS cells of all HD tissues investigated regardless of the histological subtype and the phenotype of H-RS cells (ie, CD30+/CD40+ versus CD30-/CD40+). Co-expression of CD30 and CD30L that was seen on H-RS cells of all, except the CD30- nodular lymphocyte predominant, subtypes of HD may point to the use of this pair of molecules in paracrine and/or autocrine mitogenic cell interactions. Monoclonal antibody M80 may thus represent a useful tool for studying CD30L expression on cultured cell lines and primary cells from normal, reactive, and malignant tissues.
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regulation of murine b cell growth and differentiation by CD30 Ligand
European Journal of Immunology, 1995Co-Authors: Kurt D Shanebeck, Craig A. Smith, R G Goodwin, Charles R Maliszewski, Mary K Kennedy, Kathleen S Picha, K H GrabsteinAbstract:A Ligand for CD30 has been recently cloned, and has been shown to have sequence homology with the tumor necrosis factor family of cytokines. CD30 Ligand (CD30L) was found to be induced on helper T cell clones, and its receptor was expressed on freshly isolated and activated murine B cells. Recombinant murine CD30L was found to share many functional properties with CD40 Ligand (CD40L) in the regulation of murine B cell growth and differentiation in vitro. CD30L stimulated B cell proliferation, antigen-specific antibody production, and polyclonal immunoglobulin secretion in a cytokine-dependent manner. In particular, the stimulation of B cell proliferation by CD30L required interleukin (IL)-4 and IL-5, induction of anti-sheep red blood cell antibody-secreting B cells by CD30L required IL-2 and IL-5, and optimal induction of polyclonal immunoglobulin secretion required IL-4 and IL-5. Under these conditions, the polyclonal secretion of IgG1, IgA, IgG3 and IgE was induced. The induction of immunoglobulin secretion by CD30L was independent of CD40L, as B cells from CD40L deficient-mice responded normally to CD30L treatment. We conclude that CD30L is a potent mediator of B cell growth and differentiation in vitro and may play a role in cognate T cell-B cell interactions.
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Pleiotropic effects of the CD30 Ligand on CD30-expressing cells and lymphoma cell lines
Blood, 1994Co-Authors: Hans-jorgen Gruss, Craig A. Smith, Norman Boiani, Douglas E. Williams, Richard J. Armitage, Raymond G. GoodwinAbstract:CD30 is a member of the tumor necrosis factor receptor superfamily. CD30 was originally described as a cell surface antigen on primary and cultured Hodgkin's and Reed-Sternberg cells. In this study, recombinant human CD30 Ligand was expressed on the surface of CV-1/EBNA cells and tested for biologic activities on a variety of different CD30+ human lymphoma cell lines. CD30 Ligand enhanced Ig secretion of Epstein-Barr virus (EBV)-immortalized, CD30+ lymphoblastoid B-cell lines, but not Burkitt lymphoma lines. Recombinant CD30 Ligand enhanced proliferation of "T-cell-like" Hodgkin's disease-derived cell lines and an adult T-cell leukemia cell line, but not "B-cell-like" Hodgkin's disease-derived cell lines, CD30+, EBV-immortalized lymphoblastoid B-cell lines, or CD30+ and EBV+ tumor B-cell non-Hodgkin's lymphoma cell lines. In addition, CD30 Ligand mediated reduction of proliferation and viability, by induction of cytolytic cell death, of CD30+, large-cell anaplastic lymphoma cell lines. Two new antibodies, M44 and M67, against the CD30 antigen demonstrated similar biologic activities to the CD30 Ligand. Taken together, these data demonstrate pleiotropic biologic activities of the CD30 Ligand on different CD30+ lymphoma cell lines and indicate that the CD30-CD30 Ligand interaction might have a pathophysiologic role in Hodgkin's and some non-Hodgkin's lymphomas.
Peter J L Lane - One of the best experts on this subject based on the ideXlab platform.
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concurrent ox40 and CD30 Ligand blockade abrogates the cd4 driven autoimmunity associated with ctla4 and pd1 blockade while preserving excellent anti cd8 tumor immunity
Journal of Immunology, 2017Co-Authors: Maher G Nawaf, Hideo Yagita, Fabrina Gaspal, Fiona M Mcconnell, Maria H Ulvmar, David R Withers, Gwilym J Webb, Nick D Jones, James P Allison, Peter J L LaneAbstract:Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans ...
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ox40 Ligand and CD30 Ligand are expressed on adult but not neonatal cd4 cd3 inducer cells evidence that il 7 signals regulate CD30 Ligand but not ox40 Ligand expression
Journal of Immunology, 2005Co-Authors: Miyeon Kim, Graham Anderson, Andrea J White, Eric J Jenkinson, Wiebke Arlt, Ingalill Martensson, Lena Erlandsson, Peter J L LaneAbstract:In this report, we have examined the expression of the T cell survival signals, OX40 Ligand (OX40L) and CD30 Ligand (CD30L) on CD4+CD3−CD11c−B220−IL-7Rα+ inducer cells from birth to adulthood in mice. We found that adult but not neonatal inducer cells expressed high levels of OX40L and CD30L, whereas their expression of TNF-related activation-induced cytokine (TRANCE) and receptor activator of NF-κB (RANK) was comparable. The failure of neonatal inducer cells to express the Ligands that rescue T cells helps to explain why exposure to Ag in neonatal life induces tolerance rather than immunity. The expression of OX40L and CD30L on inducer cells increased gradually in the first few weeks of life achieving essentially normal levels around the time mice were weaned. We found that IL-7 signaling through the common cytokine receptor γ-chain was critical for the optimal expression of both TNF-related activation-induced cytokine and CD30L but not OX40L. Furthermore, glucocorticoids, which potently suppress T effector function, did not influence the expression of OX40L and CD30L in the presence of IL-7.
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mice deficient in ox40 and CD30 signals lack memory antibody responses because of deficient cd4 t cell memory
Journal of Immunology, 2005Co-Authors: Fabrina Gaspal, Miyeon Kim, Fiona M Mcconnell, Chandra Raykundalia, Vasilios Bekiaris, Peter J L LaneAbstract:Recently, we reported that a CD4 + CD3 − CD11c − accessory cell provided OX40-dependent survival signals to follicular T cells. These accessory cells express both OX40 Ligand and CD30 Ligand, and the receptors, OX40 and CD30, are both expressed on Th2-primed CD4 T cells. OX40 and CD30 signals share common signaling pathways, suggesting that CD30 signals might substantially compensate in OX40-deficient mice. In this report we have dissected the signaling roles of CD30 alone and in combination with OX40. CD30-deficient mice showed an impaired capacity to sustain follicular germinal center responses, and recall memory Ab responses were substantially reduced. Deficiencies in OX40 and CD30 signals were additive; secondary Ab responses were ablated in double-deficient mice. Although the initial proliferation of OX40/CD30 double-knockout OTII transgenic T cells was comparable to that of their normal counterparts, they failed to survive in vivo, and this was associated with reduced T cell numbers associated with CD4 + CD3 − cells in B follicles. Finally, we show that OX40/CD30 double-knockout OTII transgenic T cells fail to survive compared with normal T cells when cocultured with CD4 + CD3 − cells in vitro.
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cd4 cd3 accessory cells costimulate primed cd4 t cells through ox40 and CD30 at sites where t cells collaborate with b cells
Immunity, 2003Co-Authors: Miyeon Kim, Fabrina Gaspal, Helen E Wiggett, Fiona M Mcconnell, Adam Gulbransonjudge, Chandra Raykundalia, Lucy S K Walker, Margaret Goodall, Peter J L LaneAbstract:Abstract In this report we identify an accessory cell that interacts with primed and memory T cells at sites where they collaborate with B cells. These cells are distinguished from conventional dendritic cells by their lack of response to Flt3 Ligand and their inability to process antigen. Unlike dendritic cells, the CD4 + CD3 − cells have little CD80 or CD86 expression but do express high levels of the TNF Ligands, OX40 Ligand and CD30 Ligand. We show that Th2-primed cells express the receptors for these TNF Ligands and preferentially survive when cocultured with these cells. Furthermore, we show that the preferential survival of OX40 + T cells and support of memory T cell help for B cells are linked to their association with CD4 + CD3 − cells in vivo.