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L20. Two stage model for
induction of autoimmunity: SEB synergises with interferon-gamma to induce
alopecia areata. Introduction:. It was hypothesized that autoimmune T-cell diseases require two conditions, loss of tolerance to induce autoreactive T-cells, and a stimulus, such as superantigen, to expand the autoreactive T-cells. Alopecia areata (AA) is associated with loss of immune privilege in hair follicles It was proposed that treatment with Staphylococcal Enterotoxin B (SEB) superantigen would expand autoreactive T-cells and synergize with INF-g to induce alopecia areata (AA) in C3H/HeJ mice. Method: C3H/HeJ mice 7 wk old were injected IV with murine IFN-g 2 x 104 U or PBS for three consecutive days, followed by injections every 7 days. 30 days following the first injection, , the female and male mice were divided into three groups: Group 1: (PBS alone)Mice injected with PBS for 30 days received additional PBS injections IV for 2 consecutive days followed by injections with PBS every 7 days. Group 2: (INF-g alone) Mice treated 30 days with INF-g were injected IV with IFN-g for two days and followed by every 7 days. Group 3: (INF-g & SEB) Treated 30 days with INF-g, injected intraperitoneal with SEB (50 mg) for 2 days followed by injections with INF-g every 7 days. Mice were examined for hair loss. Skin was harvested 14 wks after the first injection and analyzed by histology as well as immunohistochemistry for ICAM-1, and MHC class I & II. Results: Clinical rates of AA development on back and abdomen of C3H/HeJ mice; Group 1: PBS alone 7% (1/14), Group 2: INF-g alone 23.5% (4/17), Group 3: ING-g + SEB 60% (9/15), (p<0.05 for Group 3 vs. Group 1.). INF-g plus SEB was superior to INF-g alone in inducing AA in a susceptible mouse strain. Conclusion: This supports the hypothesis of a two stage model for development of autoimmune disease. |
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