Prevention of experimental autoimmune uveoretinitis by intrathymic S-antigen injection

The objective of this paper was to determine whether intrathymic injection of retinal S-antigen (S-Ag) can prevent experimental autoimmune uveoretinitis (EAU) in Lewis rats. Lewis rats were injected intrathymically with 25-100 micrograms of S-Ag in 100 microliters split between thymic lobes. Controls received vehicle alone (PBS) or 100 micrograms of BSA. Animals were immunized two weeks later with 100 micrograms of S-Ag in CFA with or without pertussis toxin (0.5 micrograms/rat). Clinical ocular disease was confirmed by histopathology. Splenocytes and lymph node cells were assayed, in vitro, for their ability to proliferate in response to various concentrations of S-Ag. Furthermore, attempts were made to adoptively transfer protection to naive rats using spleen cells from intrathymically injected animals and to adoptively transfer EAU to protected rats using Con A activated cells from affected animals. Intrathymic injection of S-Ag reduced the incidence of EAU in animals subsequently immunized with S-Ag and pertussis, and prevented it entirely in rats immunized in the absence of pertussis. Splenic and lymph node cells from intrathymically injected animals showed reduced reactivity to S-Ag compared to controls, suggesting that intrathymic S-Ag injection may have rendered them tolerant to this antigen. We were unable to adoptively transfer protection to naive rats, nor were intrathymically injected rats protected from EAU induced by the adoptive transfer of primed lymph node cells. These data demonstrate that intrathymic S-Ag injection can be an effective method for protection from EAU, apparently through the induction of immunological tolerance and not active suppression. The tolerance was not absolute and could be overcome by increasing the intensity of the antigenic challenge.