061 Histologic and ultrastructural features of alopecia areata in C3H/HeJ mice

K.J. McElwee1,2, K. Silva2, D. Boggess2, L. Bechtold2, R. Hoffmann1, L.E. King Jr3, and J.P. Sundberg2 Dept. of Dermatology, Philipp University, Marburg, Germany1. The Jackson Laboratory, Bar Harbor, ME, USA2. Dept. of Dermatology, Vanderbilt University, Nashville, TN, USA3.

Alopecia areata (AA) can be induced in C3H/HeJ mice by grafting AA affected skin. An 8-12 week delay between surgery and overt hair loss onset provides an opportunity to examine disease pathogenesis. Normal haired C3H/HeJ mice were sham grafted or grafted with AA affected skin. Mice were euthanized at 2, 4, 6, 8, 10, and 12 weeks post surgery along with chronic AA-affected mice as a positive control. Until 6 weeks post grafting, inflammation was only evident around anagen stage hair follicles in host skin adjacent to, but not distant from, the AA affected graft. From 8 weeks AA grafted mice, but not sham grafted mice, exhibited a diffuse dermal inflammation at distant sites that progressively focused on anagen stage hair follicles at 10 and 12 weeks. Peri-follicular inflammation was primarily composed of CD4+ and CD8+ cells associated with follicular epithelium ICAM-1 expression. Only CD8+ cells penetrated intrafollicularly by 12 weeks post surgery, although both CD4+ and CD8+ intra-follicular cells were observed in chronic AA affected mice. By electron microcscopy, intra-follicular lymphocyte and macrophage infiltration was prominent by 10 weeks post surgery, primarily within the differentiating outer and inner root sheaths associated with hair follicle dystrophy. This time course study illustrates that focal follicular inflammation may develop some time in advance of overt hair loss and focuses on the differentiating root sheaths in C3H/HeJ mice. The severity of inflammation and the degree of hair follicle dystrophy induced by the infiltrate appears to reach a threshold level before overt hair loss occurs. The root sheath focus of intra-follicular inflammatory infiltration of C3H/HeJ mice suggests candidate stimulatory antigens for AA activation may be present within these morphological structures.