The potential role of cytokines and T cells in alopecia areata.

T cells play an important role in alopecia areata (AA) because AA can be reinduced by the injection of hair follicle-specific CD8+ T cells into AA scalp biopsies, which were grafted onto scid mice, and the depletion of CD8+ T cells restores hair growth in the Dundee experimental bald rat. Moreover, AA can be transferred by grafting of alopecic skin from C3H/HeJ mice with AA-like hair loss onto unaffected littermates, but the onset of AA is inhibited by i.p. injection of anti-CD44v10 antibodies. Interestingly, grafted anti-CD44v10-treated mice have decreased numbers of CD8+ T cells within the skin. Beside T cells several clinical and experimental data point towards cytokines that might be crucial inducers of hair loss in AA. An aberrant expression of cytokines of the Thl type and IL-1beta has been detected in scalp areas involved by AA, and polymorphisms of cytokine genes such as IL-1-receptor antagonist, IL-1alpha, and TNF-alpha have been shown to determine disease susceptibility and severity. Moreover, IL-1 has been shown to be a potent inhibitor of human hair growth in vitro. Such IL-1-incubated hair follicles show ultrastructural changes similar to those observable in vivo. On the other hand mice transgenic for IL-1alpha develop patchy hair loss and during the depilation-induced hair cycle in C57/BL6 mice, members of the IL-1 family are overexpressed with the onset of spontaneous catagen. Taking all of the presently available data together, we may hypothesize that CD8+ T cells are of crucial importance in AA by their interaction with MHC-I restricted autoantigens, and cytolysis of their target cells. Hair loss, however, may occur because proinflammatory cytokines may interfere with the hair cycle leading to premature arrest of hair cycling.