Instruction of naive CD4 super(+) T-cell fate to T-bet expression and T helper 1 development: roles of T-cell receptor-mediated signals

• Published in: Immunology Vol. 122; no. 2; pp. 210 - 221
• Main Authors: Ariga, Haruyuki, Shimohakamada, Yoko, Nakada, Makiyo, Tokunaga, Takeshi, Kikuchi, Takeshi, Kariyone, Ai, Tamura, Toshiki, Takatsu, Kiyoshi
• Format: Journal Article
• Language: English
• Published: 01.10.2007
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2007.02630.x

Using T-cell receptor (TCR) transgenic mice, we demonstrate that TCR stimulation of naive CD4 super(+) T cells induces transient T-bet expression, interleukin (IL)-12 receptor beta 2 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 super(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 super(---) naive CD4 super(+) T cells are stimulated through TCR in the absence of IFN- gamma or IL-12. Stimulation of naive CD4 super(+) 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 super(+) T cells to Th1 cells.