Immunohistological study of the development of the cellular infiltrate in the pelage follicles of the DEBR model for alopecia areata.

The Dundee experimental bald rat (DEBR) undergoes hair loss associated with perifollicular infiltrates of mononuclear cells (MNC), a pathological characteristic of human alopecia areata (AA). To investigate further the pathogenesis of the disease in this animal model, we have studied the development, composition and extent of the perifollicular MNC infiltration in young (6-week-old), prelesional (3-month-old), active lesional, and established lesional DEBR rats, using 6-week- and 6-month-old Wistar rats as normal controls. The proportions of hair follicles showing infiltration by MNC and their main subsets were determined using immunohistochemical staining of serial cryostat sections of flank skin biopsies. There was a good correlation between the degree of leucocyte (OX-1+) infiltration of anagen hair follicles and the development of hair loss. In 6-week-old DEBR skin, there were few perifollicular cells expressing MHC class II, with positively stained dendritic cells in the dermis above the sebaceous gland. There was a sparse perifollicular distribution of CD4+ cells (W3/25) and macrophages (ED-1+). No CD8+ cells (OX-8+) were seen associated with DEBR hair follicles, and only small numbers were present in Wistar rats. In prelesional DEBR rats there was an increased perifollicular presence of MHC class II+ cells, macrophages, and particularly of CD8+ cells, with little change in CD4+ cells. Active and established lesional rats, i.e. animals with overt loss of hair, showed a significant increase in the degree of MNC infiltration and the proportion of infiltrated follicles, the majority of which were in dystrophic anagen. In the perifollicular infiltrate the CD4+:CD8+ ratio was approximately 2:1. An intrafollicular infiltrate was prominent, and was composed of CD8+ cells and macrophages, with bulbar and suprabulbar keratinocytes expressing MHC class II antigens. CD4+ cells were not detected in follicular epithelium. ICAM-1 expression correlated with MNC infiltration. These results show marked similarities to lesional human AA. They also focus on a possible active role for CD8+ cells in the pathogenesis of hair loss in the DEBR rat.