Instruction of Naive Cd4+ T-cell Fate to T-bet Expression and T Helper 1 Development: Roles of T-cell Receptor-mediated Signals.
From: Division of Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. arigah-in@tokyo-hosp.jp
Immunology
- Publish Date: Oct 2007
- ISSN: 0019-2805
- Volume: 122
- Issue: 2
- Pages: 210-21
- Medium: Print
- Language: English
- Citation (JAMA): Ariga Haruyuki, Shimohakamada Yoko, Nakada Makiyo, et al. Instruction of Naive Cd4+ T-cell Fate to T-bet Expression and T Helper 1 Development: Roles of T-cell Receptor-mediated Signals.. Immunology Oct 2007;122:210-21
Abstract
Using T-cell receptor (TCR) transgenic mice, we demonstrate that TCR stimulation of naive CD4(+) T cells induces transient T-bet expression, interleukin (IL)-12 receptor beta2 up-regulation, and GATA-3 down-regulation, which leads to T helper (Th)1 differentiation even when the cells are stimulated with peptide-loaded I-A(b)-transfected Chinese hamster ovary cells in the absence of interferon-gamma (IFN-gamma) and IL-12. Sustained IFN-gamma and IL-12 stimulation augments naive T-cell differentiation into Th1 cells. Intriguingly, a significant Th1 response is observed even when T-bet(-/-) naive CD4(+) T cells are stimulated through TCR in the absence of IFN-gamma or IL-12. Stimulation of naive CD4(+) T cells in the absence of IFN-gamma or IL-12 with altered peptide ligand, whose avidity to the TCR is lower than that of original peptide, fails to up-regulate transient T-bet expression, sustains GATA-3 expression, and induces differentiation into Th2 cells. These results support the notion that direct interaction between TCR and peptide-loaded antigen-presenting cells, even in the absence of T-bet expression and costimulatory signals, primarily determine the fate of naive CD4(+) T cells to Th1 cells.
Mesh Headings (Keywords): Animals, Antigen-Presenting Cells, CD4-Positive T-Lymphocytes, CHO Cells, Cell Differentiation, Cell Proliferation, Cells, Cultured, Cricetinae, Cricetulus, Interferon Type II, Interleukin-12, Mice, Mice, Inbred C57BL, Mice, Transgenic, Peptide Fragments, Polymerase Chain Reaction, Receptors, Antigen, T-Cell, Signal Transduction, Spleen, T-Box Domain Proteins, Th1 Cells
Check for Full Text / PubMed Unique Identifier (PMID): 17490433
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