Antigen Specific Tolerance Inhibits Autoimmune Uveitis in Pre-sensitized Animals via Deletion and CD4(+)CD25(+) T-Regulatory Cells

The objective of the present study was to inhibit experimental autoimmune anterior uveitis (EAAU) by establishing antigen specific immune tolerance in animals pre-sensitized with melanin associated antigen (MAA). Intravenous administration of MAA on day 6, 7, 8 and 9 post-immunization induced tolerance and inhibited EAAU in all Lewis rats. Number of cells (total T cells, CD4(+) T cells and CD8(+) T cells) undergoing apoptosis dramatically increased in the popliteal lymph nodes (LNs) of the tolerized animals compared to non-tolerized animals. Additionally, FasL, TNFR1 and caspase-8 were upregulated in tolerized rats. Proliferation of total lymphocytes, CD4(+)T cells and CD8+ T cells (harvested from the popliteal LNs) in response to antigenic stimulation was drastically reduced in the state of tolerance compared to the cells from non-tolerized animals. Level of IFN-γ and IL-2 decreased while TGF-β2 was elevated in the state of tolerance. Furthermore, the number of CD4(+)CD25(+)FoxP3(+) Tregs increased in the popliteal LNs of tolerized animals compared to non-tolerized animals. In conclusion, our results suggest that deletion of antigen specific T cells via apoptosis and active suppression mediated by Tregs plays an important role in the induction of antigen specific immune tolerance in animals with an established immune response against MAA.