Role of IFN-γ in the establishment of anterior chamber-associated immune deviation (ACAID)-induced CD8 + T regulatory cells

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Abstract

ntroduction of alloantigens into the AC induces a form of immune tolerance known as ACAID, which induces antigen-specific CD8 + Tregs, contributing to ocular immune privilege by down-regulating immune responses. Recent evidence suggests IFN-γ is needed for the suppressive function of CD8 + ACAID Tregs. This study tested the hypothesis that IFN-γ is needed for alloantigen-specific ACAID CD8 + Tregs to execute their suppressive function but is not required for the establishment of ACAID CD8 + Tregs. To address this hypothesis, ACAID was induced by injecting BALB/c spleen cells into the AC of WT C57BL/6 mice, IFN-γ -/- C57BL/6 mice, or anti-IFN-γ-treated WT C57BL/6 mice. LAT assays using C57BL/6 APCs as stimulators, CD4 + T cells from C57BL/6 mice previously immunized toward BALB/c alloantigens as effector cells, and IFN-γ-competent, IFN-γ -/-, or IFN-γR -/- CD8 + Tregs were used to evaluate the suppressive function of CD8 + ACAID Tregs in response to IFN-γ. IFN-γ -/- mice or mice treated with anti-IFN-γ antibody prior to AC injection of alloantigen failed to develop ACAID. The suppressive function of IFN-γ -/- ACAID CD8 + Tregs was restored through the administration of exogenous IFN-γ. This suppressive responsiveness toward IFN-γ was CD8 + Treg-intrinsic, as CD8 + Tregs from IFN-γR -/- mice, which were primed in the AC with alloantigens, were not able to suppress alloantigen-specific DTH responses. These results indicate that IFN-γ is not needed for the induction of CD8 + ACAID Tregs but is required for ACAID Tregs to exert the suppression of allospecific DTH responses.

Original languageEnglish (US)
Pages (from-to)475-483
Number of pages9
JournalJournal of Leukocyte Biology
Volume91
Issue number3
DOIs
Publication statusPublished - Mar 2012

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Keywords

  • Anterior chamber
  • Eye
  • Immune privilege
  • Interferon-gamma
  • Local adoptive transfer

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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