In vitro-induced cell-mediated immune deviation to encephalitogenic antigens

The injection of antigens into the Anterior Chamber (AC) of the eye induces Anterior Chamber Associated Immune Deviation (ACAID), which is a potent form of immune deviation that is largely attributed to the effect of TGF beta 2 in the aqueous humor on ocular antigen-presenting cells (APCs). ACAID antigen presentation via APCs and B cells leads to the generation of antigen-specific T regulatory cells. The encephalitogenic antigens Myelin oligodendrocyte glycoprotein (MOG) and Myelin basic protein (MBP) have an obvious clinical relevance. We hypothesized that the intravenous injection of in vitro-generated ACAID APCs or in vitro-generated ACAID B cells specific to the encephalitogenic antigens MOG(35-55)/MBP induces specific peripheral tolerance in recipient BALB/c mice. We examined the suppression of MOG(35-55)-specific/MBP-specific inflammatory responses using delayed-type hypersensitivity (DTH) assays and Local Adoptive Transfer (LAT) assays. Results indicated that MOG(35-55)-specific/MBP-specific tolerance was generated after the intravenous injections of MOG(35-55)-specific/MBP-specific ACAID APCs, MOG(35-55)-specific/MBP-specific ACAID B cells, and MOG(35-55)-specific/MBP-specific ACAID T regulatory cells. The specific immune deviation was in vitro-induced, cell-mediated, and specific to the encephalitogenic antigens MOG(35-55)/MBP. This in vitro-mediated approach for the generation of MOG(35-55)/MBP-specific tolerance opens up avenues for the application of ACAID as a tool for the therapy of Multiple Sclerosis, Schizophrenia, and other diseases. (C) 2013 Elsevier Inc. All rights reserved.