News on Alopecia Areata

Two stage model for induction of autoimmunity: SEB synergizes with interferon-gamma to induce alopecia areata
A. Gilhar*, B. Assy*, R. S. Kalish**
*Skin Research Laboratory, The B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, and Flieman Medical Center, Haifa, Israel
**Dept of Dermatology, SUNY at Stony Brook, New York, USA

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. We previously demonstrated that interferon-gamma (INF-g) induces expression of MHC class I and II, resulting in loss of immune privilege and induction of AA in genetically susceptible female C3H/HeJ mice. It was proposed that treatment with Staphylococcal Enterotoxin B (SEB) superantigen would expand autoreactive T-cells and synergize with INF-g to induce AA. C3H/He 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 skin and analyzed by histology as well as immunohistochemistry for ICAM-1, and MHC class I & II. Clinical rates of AA development on back and abdomen of C3H/He male mice; Group 1: PBS alone 7% (1/14), Group 2: INF-g alone 17% (3/17), Group 3: ING-g + SEB 46% (7/15), (p<0.05 for Group 3 vs. Group 1). Female mice did not demonstrate a difference between INF-G and (INF-g + SEB). INF-g plus SEB was superior to INF-g alone in inducing AA in a susceptible mouse strain. This supports the hypothesis of a two stage model for development of autoimmune disease.