International Immunology, Vol. 14, No. 8, pp. 943-951,
August 2002
© 2002 Japanese Society for Immunology
FEATURED ARTICLE OF THE MONTH |
Th1/Th2 cell differentiation of developing CD4 single-positive thymocytes
Departments of 1 Molecular Immunology and 2 Medical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan 3 Life Science Group, Hitachi Ltd, Kawagoe, Saitama 350-1165, Japan 4 PRESTO, Japan Science and Technology Corporation (JST), 5 Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, and 6 Department of Applied Biology, Faculty of Science and Technology, Science University of Tokyo, 2641 Yamazaki, Chiba 278-8510, Japan
The first two authors contributed equally to this work
Correspondence to: T. Nakayama, Department of Medical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260, Japan. E-mail: nakayama{at}med.m.chiba-u.ac.jp
Transmitting editor: A. Singer
In this study we investigate the stage at which developing T cells in the thymus acquire the ability to differentiate into Th1 and Th2 cells. We addressed this question by using sorted heat-stable antigen (HSA)+ and HSA– CD4 single-positive (SP) thymocytes prepared from ovalbumin-specific TCR
ß transgenic mice and an in vitro Th1/Th2 differentiation culture system. HSA– CD4 SP thymocytes show nearly full functional capacity to differentiate into either Th1 or Th2 cells. A dramatic difference was observed, however, between HSA+ and HSA– CD4 SP thymocytes in the efficiency for Th1 cell differentiation. TCR function of HSA+ CD4 SP thymocytes appeared to be fully developed because antigen-induced proliferation and IL-2 production were essentially equivalent to that of HSA– CD4 SP thymocytes. However, the levels in IL-12 receptor (IL-12R) ß2 chain expression following anti-TCR stimulation were dramatically low in the HSA+ CD4 SP thymocytes. Decreased IL-12-induced STAT4 phosphorylation was also observed. Moreover, IL-12-dependent transcriptional up-regulation of T-bet and STAT4 was deficient in the HSA+ CD4 SP thymocytes. Thus, the poor capacity of HSA+ CD4 SP thymocytes to proceed to Th1 cell differentiation appears to be at least partly due to underdeveloped capacity in IL-12R expression and function.
Keywords: CD4 single-positive thymocyte, IL-12 receptor, STAT4, Th1/Th2
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