Induction of cellular immunity against hair follicle melanocyte causes alopecia

Abstract

Alopecia areata (AA) is generally regarded as an organ-specific autoimmune disease. Although it has been hypothesized that the autoimmunity is mediated by T cells and that hair follicle melanocyte is one of the targets, definitive evidence is lacking. We here demonstrate that AA-like lesions can be induced in mice by inducing CD8(+) T-cell-mediated immunity to hair follicle melanocytes. We found that hair loss was induced in mice-bearing interleukin-12-producing B16 melanoma cells by the depletion of CD4(+) T cells, accompanied by vitiligo-like coat color change. The alopecic lesions varied in size from pachy to extensive. In many instances, hair loss developed and was followed by the regrowth of white hairs. Histological analysis revealed that mononuclear cells infiltrated in and around the bulb region of hair follicles. Furthermore, immunohistochemical examination clearly showed the intra-follicular infiltration of CD8(+) T cells. Neither the vitiligo-like coat color nor AA-like lesions were induced when CD8(+) T cells were codepleted. These observations indicate that the induction of CD8(+) T-cell-mediated immunity against hair follicle melanocytes causes alopecia. It is thought that there are many types of AA with different mechanisms, targets etc. Although hair follicle melanocytes have long been thought to be one of the targets of AA, evidence to support the hypothesis is sparse. Therefore, we believe that our observation is significant to support the hypothesis.

Abnormal Interactions between Perifollicular Mast Cells and CD8+ T-Cells May Contribute to the Pathogenesis of Alopecia Areata

“…As expected from the literature [14], [19], [21], [24], [78], [79], the number of CD8+ T-cells in the perifollicular mesenchyme was significantly higher in lesional compared to non-lesional AA (data not shown) and to healthy anagen HFs (Figure 3A–C). …”

T-Cell Reconstitution after Thymus Xenotransplantation Induces Hair Depigmentation and Loss

“…Our data support the established hypothesis that autoimmune hair loss and depigmentation are T cell–mediated and suggest that these disorders can share a common pathogenesis, as previously reported in mice (Nagai et al , 2006) and chickens (Smyth and McNeil, 1999). Although there are clinical reports of coincidence of alopecia areata and vitiligo (Dhar and Kanwar, 1994; Adams and Lucky, 1999; Tan et al , 2002; Yadav et al , 2009; Akay et al , 2010; Ramot et al , 2010), the link between the two diseases is controversial, with some studies finding no association (Majumder et al , 1993).…”

Childhood alopecia areata—Data from the National Alopecia Areata Registry

“…Using ultrastructural observations of the hair bulb, Tobin and colleagues demonstrated that melanocytes could be specifically damaged in acute AA . Further evidence for this hypothesis was presented in an animal model, in which induced CD8 + T‐cell‐mediated immunity to hair follicle melanocytes resulted in a vitiligo‐like coat color change upon regrowth …”