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

Details

Serval ID
serval:BIB_DCBC17CB2BE7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Central role for TCR/CD3 ligation in the differentiation of CD4+ T cells toward A Th1 or Th2 functional phenotype
Journal
Journal of Immunology
Author(s)
Rocken  M., Muller  K. M., Saurat  J. H., Muller  I., Louis  J. A., Cerottini  J. C., Hauser  C.
ISSN
0022-1767 (Print)
Publication state
Published
Issued date
01/1992
Volume
148
Number
1
Pages
47-54
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan 1
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
Animals Antigens, CD3 Antigens, Differentiation, T-Lymphocyte/*physiology Antigens, Surface/immunology Antigens, Thy-1 B-Lymphocytes/immunology CD4-Positive T-Lymphocytes/cytology/*physiology Cell Differentiation Enterotoxins/immunology Female Immunologic Memory Interferon Type II/immunology Interleukin-2/metabolism/pharmacology Interleukin-4/metabolism Lymphocyte Activation Lymphokines/biosynthesis Mice Mice, Inbred BALB C Receptors, Antigen, T-Cell/*physiology Receptors, Antigen, T-Cell, alpha-beta/*physiology T-Lymphocytes, Helper-Inducer/*cytology
Pubmed
Web of science
Create date
28/01/2008 11:13
Last modification date
20/08/2019 16:01
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