Abstract
Epidemiological data indicate that infections play a role in preventing autoimmunity. Thus, the decline in the incidences of infectious diseases and the increase in the frequency of autoimmune diseases also known as the hygiene hypothesis suggest that there might be a link between the two phenomena. In this study using the iFABP-Ova transgenic mouse model, that expresses ovalbumin in the small intestine, we showed that prior LCMV infection dampened self-reactive effector CD8 T cell responses and protected mice from enteric autoimmunity. LCMV specific memory CD8 T cells, generated after infection, were not required for this protection as elimination of these cells using a depleting antibody still protected the mice from enteric autoimmunity. Moreover, we found that infection induced suppression is specific to self antigen reactive CD8 T cells without affecting foreign antigen specific CD8 T cell responses. Lastly, we found that a similar suppression of self-reactive CD8 T cells occurs in iFABP-Ova mice when tolerant CD8 T cells are previously present. Thus there might be some similarities in the mechanism of suppression of self-reactive CD8 T cells by viral infections and tolerance generation. Taken together these data demonstrate that prior viral infections or tolerant CD8 T cells have the ability to suppress self-reactive autoimmune responses and provide protective effects without compromising immunity to foreign pathogens.
