Anterior Chamber–Associated Immune Deviation (ACAID) Depends on DAF and CD59 Activities

Abstract

Abstract: : Purpose: Localized suppression of immune responses in the anterior chamber (a.c.), a phenomenon termed anterior chamber–associated immune deviation (ACAID), underlies the "immune privileged" state in the eye. Experimentally, ACAID is demonstrable by findings that antigen preinjected into the a.c. suppresses Th–1 immune responses eventuating from subsequent systemic immunization. To study the importance of DAF and CD59 in the induction of ACAID, we performed a.c. preinjection of ovalbumin (OVA) in Daf1^–/–, CD59^–/–, Daf1^–/–CD59a^–/–, and wild type (wt) mice, after which we evaluated induction of anti–OVA T cell reactivity. Methods: Five days following a.c. preinjection of OVA or PBS control in each mouse group, OVA was injected subcutaneously (s.c.) in incomplete or complete Freund’s adjuvant (IFA or CFA) and delayed–type hypersensitivity (DTH), anti–OVA IFN–γ ELISPOT recall responses and anti–OVA cytotoxic T lymphocyte (CTL), activity was measured. TGF–ß–1 levels in eyes were measured by ELISA. Results: Whereas DTH size was markedly decreased in OVA a.c. preinjected wt mice (characteristic of ACAID), no suppressive effect was measurable in any of the knockouts. A 3–fold larger lesion developed in the all knockouts with 10–fold more histiocytes (no difference between OVA and PBS a.c. preinjected controls). While OVA a.c. preinjected wts showed minimal CD4⁺ recall responses in IFN–γ ELISPOTs, all of the OVA a.c. preinjected knockouts conversely showed exaggerated responses over their PBS a.c. preinjected counterparts. Similarly, while OVA a.c. preinjected wt mice showed complete loss of CTL reactivity of both their lymph node and splenic T cells, none of the OVA a.c. preinjected knockouts showed a significant decrease compared to PBS controls. ELISAs of OVA a.c. preinjected eyes showed increased levels in wts but not in knockouts. Conclusions: DAF and CD59 are critical in conferring immune privilege. This result raises the possibility that the purified regulators could have value in "high risk" corneal transplants and possibly other immune–mediated eye diseases.

Keywords: ACAID • transplantation • autoimmune disease