Th1/Th2 cell differentiation of developing CD4 single‐positive thymocytes

• Published in: International immunology 2002-08, Vol.14 (8), p.943-951
• Main Authors: Kikkawa, Emiko, Yamashita, Masakatsu, Kimura, Motoko, Omori, Miyuki, Sugaya, Kaoru, Shimizu, Chiori, Katsumoto, Takuo, Ikekita, Masahiko, Taniguchi, Masaru, Nakayama, Toshinori
• Format: Article
• Language: English
• Subjects: CD4 single‐positive thymocyte; IL‐12 receptor; STAT4; Th1/Th2
• ISSN: 0953-8178; 1460-2377; 1460-2377
• DOI: 10.1093/intimm/dxf057

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 TCRαβ 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) β2 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.