Premium
IFN‐γ Blocks CD4+CD25+ Tregs and Abolishes Immune Privilege of Minor Histocompatibility Mismatched Corneal Allografts
Author(s) -
Cunnusamy K.,
Niederkorn J. Y.
Publication year - 2013
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.12466
Subject(s) - minor histocompatibility antigen , immune privilege , immunology , major histocompatibility complex , medicine , corneal transplantation , il 2 receptor , interferon , histocompatibility , antigen , immune system , transplantation , t cell , human leukocyte antigen
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.