Thymic selection pathway regulates the effector function of CD4 T cells

Wei Li, M. Hanief Sofi, Norman Yeh, Sarita Sehra, Brian P. McCarthy, Dipak R. Patel, Randy R. Brutkiewicz, Mark H. Kaplan, Cheong Hee Chang

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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 γ 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. JEM

Original languageEnglish (US)
Pages (from-to)2145-2157
Number of pages13
JournalJournal of Experimental Medicine
Volume204
Issue number9
DOIs
StatePublished - Sep 3 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Li, W., Sofi, M. H., Yeh, N., Sehra, S., McCarthy, B. P., Patel, D. R., Brutkiewicz, R. R., Kaplan, M. H., & Chang, C. H. (2007). Thymic selection pathway regulates the effector function of CD4 T cells. Journal of Experimental Medicine, 204(9), 2145-2157. https://doi.org/10.1084/jem.20070321