The source of early IFN-γ that plays a role in Th1 priming

G. Das, S. Sheridan, Jr Janeway

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

When naive CD4 T cells are primed, they rapidly differentiate into polarized Th1 and/or Th2 phenotypes. A major factor in producing such polarization is the early production of cytokines (IL-12 and IFN-γ in the case of Th1 cells and IL-4 in the case of Th2 cells). One issue that remains unresolved is the source of the early IFN-γ that synergizes with IL-12 to fully polarize CD4 T cells into Th1 cells. We have examined this question by injecting mice with anti-CD3 and examining cells from normal and various MHC-knockout mice. We found that IFN-γ is induced rapidly in a small subset of CD8 T cells. This subset is absent in mice that lack β2-microglobulin, but not in KbDb-double-knockout mice, indicating that these CD8 T cells are dependent on nonclassical MHC class Ib molecules. The early burst of IFN-γ polarizes CD4 T cells toward Th1 cells, in part by stimulating the release of IL-12 from APC. We also use TAP- and CD1-knockout mice to show that such cells are not CD1-restricted NK T cells, nor are they dependent on TAP-1 transport for surface expression of the relevant MHC class Ib molecule. Therefore, they arise on MHC class Ib molecules that do not depend on TAP-1 transporters.

Original languageEnglish (US)
Pages (from-to)2004-2010
Number of pages7
JournalJournal of Immunology
Volume167
Issue number4
DOIs
StatePublished - Aug 15 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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