Altered Th1 cell differentiation programming by CIITA deficiency

Dipak R. Patel, Mark H. Kaplan, Cheong Hee Chang

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

CD4 T cell differentiation is a complex process affected by many transcription factors interacting in a tightly regulated manner. We have previously shown that CIITA-deficient mouse Th1 cells expressed Th2-type cytokines, while IFN-γ expression was normal. In this study, we show that CIITA-deficient Th1 cells contain three distinct populations: cells secreting IL-4 alone, IFN-γ alone, and both IL-4 and IFN-γ together. This novel phenotype is stable over multiple rounds of stimulation in the presence of Th1-inducing factors. CIITA-deflcient Th1 cells require TCR-mediated signaling to express Th2 cytokines, and this occurs with similar kinetics as wild-type Th2 cells. Both GATA-3 and IL-4 appear to be required for CIITA-deficient Th1 cells to express Th2-type cytokines. Interestingly, however, CIITA-deflcient Th1 cells can produce IL-4 in the absence of exogenous IL-4. Introducing either CIITA or antisense GATA-3 during Th1 differentiation partially reduces Th2-type cytokine expression. With the exception of Th2-type cytokine expression, Th1 differentiation occurs normally in the absence of CIITA, as measured by expression of T-bet, IL-12Rβ2, IL-18Rα, and IFN-γ. Therefore, CIITA plays a key role to repress Th2-type cytokine expression as naive CD4 T cells differentiate toward the Th1 lineage.

Original languageEnglish (US)
Pages (from-to)5501-5508
Number of pages8
JournalJournal of Immunology
Volume173
Issue number9
DOIs
StatePublished - Nov 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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