Allergic conjunctivitis renders CD4+ T cells resistant to T regulatory cells and exacerbates corneal allograft rejection

N. J. Reyes, P. W. Chen, J. Y. Niederkorn

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Allergic diseases rob corneal allografts of immune privilege and increase immune rejection. Corneal allograft rejection in BALB/c allergic hosts was analyzed using a short ragweed (SWR) pollen model of allergic conjunctivitis. Allergic conjunctivitis did not induce exaggerated T-cell responses to donor C57BL/6 (B6) alloantigens or stimulate cytotoxic T lymphocyte (CTL) responses. Allergic conjunctivitis did affect T regulatory cells (Tregs) that support graft survival. Exogenous IL-4, but not IL-5 or IL-13, prevented Treg suppression of CD4+ effector T cells isolated from naïve mice. However, mice with allergic conjunctivitis developed Tregs that suppressed CD4+ effector T-cell proliferation. In addition, IL-4 did not inhibit Treg suppression of IL-4Rα-/- CD4+ T-cell responses, suggesting that IL-4 rendered effector T cells resistant to Tregs. SRW-sensitized IL-4Rα-/- mice displayed the same 50% graft survival as nonallergic WT mice, that was significantly less than the 100% rejection that occurred in allergic WT hosts, supporting the role of IL-4 in the abrogation of immune privilege. Moreover, exacerbation of corneal allograft rejection in allergic mice was reversed by administering anti-IL-4 antibody. Thus, allergy-induced exacerbation of corneal graft rejection is due to the production of IL-4, which renders effector T cells resistant to Treg suppression of alloimmune responses. The exacerbation of immune rejection of corneal transplants that occurs in mice with allergic conjunctivitis is due to allergen-induced IL-4, which renders immune effector T cells resistant to the inhibitory effects of T regulatory cells.

Original languageEnglish (US)
Pages (from-to)1181-1192
Number of pages12
JournalAmerican Journal of Transplantation
Volume13
Issue number5
DOIs
StatePublished - May 1 2013

Keywords

  • Allergy
  • T regulatory cells
  • cornea
  • eye
  • tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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