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DE Faunce, J Stein-Streilein; ACAID-Like APCs Demonstrate Therapeutic Potential for Alleviating Experimental Autoimmune Encephalomyelitis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2964.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Intraocular administration of antigens leads to the induction of a form of peripheral tolerance known as Anterior Chamber Associated Immune Deviation (ACAID). ACAID is initiated at the cellular level by tolerogenic eye-derived APCs that carry antigen from the eye to the spleen where they form clusters with NKT cells and CD8 regulatory T (Tr) cells that suppress Th1 immunity. Here we tested whether in vitro-generated ACAID APCs could be used to prevent the Th1 immunity associated with experimental autoimmune encepalomyelitis (EAE), a murine model of multiple sclerosis. Methods: ACAID-like tolerogenic (and immunogenic control) APCs were generated in vitro by culturing thioglycollate elicited peritoneal exudate cells overnight with the CNS antigen MBP +/- TGFß2. Tolerogenic or control APCs were given (i.v.) to mice that received immunization with MBP in CFA (+pertussis) seven days earlier. To test whether EAE mice treated with tolerogenic APCs developed Tr cells, we collected enriched splenic T cells from APC-treated mice, transferred them to naive mice that were subsequently immunized with MBP, and monitored the mice for EAE symptoms for thirty three days. To identify whether Tr cells were CD4+ or CD8+, additional groups of mice received Tr cells that were depleted of CD4 or CD8 T cells by Ab and complement treatment. The mice that received Tr cell transfer were then immunized against MBP and monitored for EAE symptoms. Results:In vitro generated ACAID APCs pulsed with MBP decreased the severity and incidence of ongoing EAE. CD8 (but not CD4) Tr cells could be isolated from the spleens of ACAID APC-treated EAE mice and when transferred to naive mice, prevented the development of EAE. Conclusion:Cell-based therapy with MBP-pulsed ACAID tolerogenic APCs is a potential treatment for autoimmune disease of the CNS and operates through the development of CD8 Tr cells that actively suppress or prevent Th1 immunity.
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