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International Immunology Advance Access originally published online on October 11, 2004
International Immunology 2004 16(12):1691-1699; doi:10.1093/intimm/dxh170
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© 2004 The Japanese Society for Immunology

Featured Article of the Month

The role of antigenic peptide in CD4+ T helper phenotype development in a T cell receptor transgenic model

Toshiki Tamura1, Haruyuki Ariga1,3, Tatsuo Kinashi1, Shuichiro Uehara1,4, Takeshi Kikuchi1,4, Makiyo Nakada1, Takeshi Tokunaga1, Wen Xu1, Ai Kariyone1, Takashi Saito5, Toshio Kitamura2, Gavin Maxwell6, Satoshi Takaki1 and Kiyoshi Takatsu1

1 Division of Immunology and 2 Cellular Therapy and Hematopoietic Factors, Institute of Medical Science, University of Tokyo, 3 First Department of Internal Medicine, Kyorin University School of Medicine, 4 Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo and 5 Department of Molecular Genetics, Chiba University Graduate School of Medicine, Chiba, Japan
6 Babraham Institute, University of Cambridge, Cambridge, UK

Correspondence to: K. Takatsu; E-mail: takatsuk{at}ims.u-tokyo.ac.jp

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-Ab 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 ß-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-Ab 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-Ab-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-Ab and TCR may primarily influence determination of the fate of naive CD4+ T cells in their differentiation towards the Th1 subset.

Keywords: altered peptide ligand, IFN-{gamma}, Th1, Th2, Th1-inducing peptide, transgenic mouse

Transmitting editor: K. Sugamura


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