title: Allergic conjunctivitis renders CD4(+) T cells resistant to t regulatory cells and exacerbates corneal allograft rejection.
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.
authors.affiliation: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Reyes
authors.forename: P W
authors.initials: PW
authors.lastname: Chen
authors.forename: J Y
authors.initials: JY
authors.lastname: Niederkorn
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003233:Conjunctivitis, Allergic / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D003315:Cornea / Q000276:immunology; D016039:Corneal Transplantation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016207:Cytokines