| First Author | Tamura T | Year | 2004 |
| Journal | Int Immunol | Volume | 16 |
| Issue | 12 | Pages | 1691-9 |
| PubMed ID | 15477229 | Mgi Jnum | J:94023 |
| Mgi Id | MGI:3510528 | Doi | 10.1093/intimm/dxh170 |
| Citation | Tamura T, et al. (2004) The role of antigenic peptide in CD4+ T helper phenotype development in a T cell receptor transgenic model. Int Immunol 16(12):1691-9 |
| abstractText | CD4(+) Th1 cells play a critical role in the induction of cell-mediated immune responses that are important for the eradication of intracellular pathogens. Peptide-25 is the major Th1 epitope for Ag85B of Mycobacterium tuberculosis and is immunogenic in I-A(b) mice. To elucidate the role of the TCR and IFN-gamma/IL-12 signals in Th1 induction, we generated TCR transgenic mice (P25 TCR-Tg) expressing TCR alpha- and beta-chains of Peptide-25-reactive cloned T cells and analyzed Th1 development of CD4(+) T cells from P25 TCR-Tg. Naive CD4(+) T cells from P25 TCR-Tg differentiate into both Th1 and Th2 cells upon stimulation with anti-CD3. Naive CD4(+) T cells from P25 TCR-Tg preferentially develop Th1 cells upon Peptide-25 stimulation in the presence of I-A(b) splenic antigen-presenting cells under neutral conditions. In contrast, a mutant of Peptide-25 can induce solely Th2 differentiation. Peptide-25-induced Th1 differentiation is observed even in the presence of anti-IFN-gamma and anti-IL-12. Furthermore, naive CD4(+) T cells from STAT1 deficient P25 TCR-Tg also differentiate into Th1 cells upon Peptide-25 stimulation. Moreover, Peptide-25-loaded I-A(b)-transfected Chinese hamster ovary cells induce Th1 differentiation of naive CD4(+) T cells from P25 TCR-Tg in the absence of IFN-gamma or IL-12. These results imply that interaction between Peptide-25/I-A(b) and TCR may primarily influence determination of the fate of naive CD4(+) T cells in their differentiation towards the Th1 subset. |
