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Title

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

Authors
Roecken, Martin
Louis, Jacques A.
Cerottini, Jean-Charles
Published in Journal of Immunology. 1992, vol. 148, no. 1, p. 47-54
Abstract 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.
Keywords AnimalsAntigensDifferentiationT-LymphocytePhysiologyImmunologyB-LymphocytesCD3 ComplexCD4-Positive T-LymphocytesCytologyPhysiologyCell DifferentiationEnterotoxinsFemaleImmunologic MemoryInterferon-gammaInterleukin-2MetabolismPharmacologyInterleukin-4Lymphocyte ActivationLymphokinesBiosynthesisMiceReceptorsAntigenT-CellHelper-InducerThy-1 Antigens
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PMID: 1345789
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ROECKEN, Martin et al. Central role for TCR/CD3 ligation in the differentiation of CD4+ T cells toward A Th1 or Th2 functional phenotype. In: Journal of Immunology, 1992, vol. 148, n° 1, p. 47-54. https://archive-ouverte.unige.ch/unige:106687

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Deposited on : 2018-07-25

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