IFN-γ Blocks CD4+CD25+ tregs and abolishes immune privilege of minor histocompatibility mismatched corneal allografts

K. Cunnusamy, J. Y. Niederkorn

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Th1 CD4+ cells are believed to be the primary mediators of corneal allograft rejection. However, rejection of fully allogeneic C57BL/6 corneal allografts soared from 50% to 90% in both interferon-gamma (IFN-γ) -/- and anti-IFN-γ-treated BALB/c mice. In contrast, similar deficits in IFN-γ in BALB/c hosts enhanced immune privilege of BALB.B (minor histocompatibility [minor H] antigen-matched, major histocompatibility complex [MHC]-mismatched) and NZB (MHC-matched, minor H antigen-mismatched) corneal allografts - decreasing rejection from 80% to ∼20%. This effect of IFN-γ was independent of CD4+ T cell lineage commitment as both anti-IFN-γ-treated acceptor and rejector mice displayed a Th2 cytokine profile. The presence of IFN-γ prevented the generation of alloantigen-specific CD4+CD25+ T regulatory cells (Tregs) in hosts receiving either MHC only mismatched BALB.B or minor only histocompatibility (minor H)-mismatched NZB corneal allografts. Tregs in these hosts promoted corneal allograft survival by suppressing Th2 effector cells. By contrast, IFN-γ was necessary for the generation of CD4+CD25+ Tregs that prevented rejection of fully allogeneic C57BL/6 corneal allografts in BALB/c hosts. These findings suggest that MHC-matching in combination with blockade of IFN-γ holds promise as a means of enhancing corneal allograft survival. This study shows that interferon-gamma, which is normally considered a proinflammatory cytokine, is necessary for the generation of T regulatory cells and the survival of MHC-matched, minor histocompatibility-mismatched corneal allografts in mice. See editorial by Evaristo and Alegre on page 3057.

Original languageEnglish (US)
Pages (from-to)3076-3084
Number of pages9
JournalAmerican Journal of Transplantation
Volume13
Issue number12
DOIs
StatePublished - Dec 1 2013

Keywords

  • Cornea
  • IFN-γ
  • Immune privilege
  • Keratoplasty
  • Tregs

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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