Central role for TCR/CD3 ligation in the differentiation of CD4+ T cells toward A Th1 or Th2 functional phenotype

Article Article scientifique Article Central role for TCR/CD3 ligation in the differentiation of CD4+ T cells toward A Th1 or Th2 functional phenotype eng 1992 author Roecken Martin author Mueller Kai Michael 23318 author Saurat Jean-Hilaire 21995 author Mueller Ingrid Ursula 62506 author Louis Jacques A. author Cerottini Jean-Charles author Hauser Conrad 22348 47-54 1345789 0022-1767 http://www.jimmunol.org/content/jimmunol/148/1/47.full.pdf Activated CD4+ T cells can be classified into distinct subsets; the most divergent among them may be considered to be the IL-2 and IFN-gamma-producing Th1 clones and the IL-4 and IL-5-producing Th2 clones. Because Th1 and Th2 clones can usually be detected only after several months of culture, we used conditions that modulate the IL-2 and IL-4 production in short term culture. Here we show that freshly isolated and subsequently in vitro-activated CD4+ T cells that were cultured for 11 days with rIL-2 and restimulated showed a IFN-gamma+ IL-2+ IL-3+ IL-4- IL-5- pattern. Because these cells were not capable of providing B cell help for IgG1, IgG2a, or IgE in an APC- and TCR-dependent T-B cell assay, they expressed a phenotype typical for most Th1 clones. In contrast, activated T cells that were cultured for 11 days with IL-2 plus a mAb to CD3 and then restimulated produced a IFN-gamma- IL-2- IL-3+ IL-4+ IL-5+ pattern. These cells were capable of providing B cell help for IgG1, IgG2a, and IgE synthesis and thus presented a phenotype typical for Th2 clones. Similar results were observed when mitogenic mAb to Thy-1.2 or to framework determinants of the alpha beta TCR were used. The induction of Th1- and Th2-like cells did not depend on the relative expression of CD44 or CD45 by the T cells before activation in vitro. Because the incubation of activated T cells with anti-CD3/TCR mAb induced high unrestricted lymphokine production, the latter might be responsible for the Th2-like lymphokine pattern observed after restimulation. To address this point, TCR V beta 8+ and V beta 8- T cell blasts were co-cultured in the presence of mAb to V beta 8. After restimulation, V beta 8+ cells had a IL-4high IL-2low phenotype and V beta 8- cells had a IL-4low IL-2high phenotype. This demonstrates that TCR ligation but not lymphokines alone are capable of inducing Th2-like cells, and this points out a central role for the TCR in the generation of T cell subsets. Animals Antigens Differentiation T-Lymphocyte Physiology Immunology B-Lymphocytes CD3 Complex CD4-Positive T-Lymphocytes Cytology Physiology Cell Differentiation Enterotoxins Female Immunologic Memory Interferon-gamma Interleukin-2 Metabolism Pharmacology Interleukin-4 Lymphocyte Activation Lymphokines Biosynthesis Mice Receptors Antigen T-Cell Helper-Inducer Thy-1 Antigens Dewey 610 3 Faculté de médecine 2 false Journal of Immunology 148 1 a75f8e1e-0c8f-4b74-9083-43e250a26f71 Article (Published version) Restricted Muller_JoI_1481992047.pdf 7890387 application/pdf restrictedAccess Faculté de médecine

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Central role for TCR/CD3 ligation in the differentiation of CD4+ T cells toward A Th1 or Th2 functional phenotype	Journal of Immunology			1992	369	0

Archive ouverte UNIGE

Mueller, Ingrid Ursula