The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
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Published online August 27, 2007
doi:10.1084/jem.20070321
The Journal of Experimental Medicine, Vol. 204, No. 9, 2145-2157
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Li et al.
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ARTICLE

 Thymic selection pathway regulates the effector function of CD4 T cells

Wei Li1, M. Hanief Sofi1, Norman Yeh1, Sarita Sehra2, Brian P. McCarthy1, Dipak R. Patel3, Randy R. Brutkiewicz1,4, Mark H. Kaplan2, and Cheong-Hee Chang1,4

1 Department of Microbiology and Immunology and 2 Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202
3 Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109
4 The Walther Cancer Institute, Indianapolis, IN 46208

CORRESPONDENCE Cheong-Hee Chang: heechang{at}umich.edu

Recently, a new developmental pathway for CD4 T cells that is mediated by major histocompatibility complex class II–positive thymocytes was identified (Choi, E.Y., K.C. Jung, H.J. Park, D.H. Chung, J.S. Song, S.D. Yang, E. Simpson, and S.H. Park. 2005. Immunity. 23:387–396; Li, W., M.G. Kim, T.S. Gourley, B.P. McCarthy, D.B. Sant'angelo, and C.H. Chang. 2005. Immunity. 23:375–386). We demonstrate that thymocyte-selected CD4 (T-CD4) T cells can rapidly produce interferon {gamma} and interleukin (IL) 4 upon in vivo and in vitro T cell receptor stimulation. These T-CD4 T cells appear to be effector cells producing both T helper type 1 (Th1) and Th2 cytokines, and they maintain a potential to produce Th2 cytokines under Th1-skewing conditions in a signal transducer and activator of transcription 6–independent manner. The IL-4 mRNA level is high in CD4 single-positive thymocytes if they are selected on thymocytes, which is at least partly caused by enhanced histone acetylation of the IL-4 locus. However, mice that can generate T-CD4 T cells showed attenuated immune responses in an allergen-induced airway inflammation model, suggesting a protective role for T-CD4 T cells during an airway challenge. Our results imply that this thymic selection pathway plays an important role in determining the effector function of the resulting CD4 cells and in regulating immune response.

Abbreviations used: BALF, bronchoalveolar lavage fluid; ChIP, chromatin immunoprecipitation; CIITA, MHC class II transactivator; E-CD4, epithelial cell–selected CD4; cTEC, cortical TEC; H&E, hematoxylin and eosin; ICS, intracellular cytokine stating; IE, intronic enhancer; SP, single positive; T-CD4, thymocyte-selected CD4; TEC, thymic epithelial cell.


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