Resident Memory T Cells and their Function in Vitiligo
The risk of repigmentation relapse in vitiligo lesions is common and occurs within the first year following treatment cessation [94]. To date, there is no treatment to prevent relapses. One study showed that vitiligo patients treated with narrow band-ultraviolet B (NB-UVB) lost their new pigment two years after cessation of treatment [95]. Notably, relapse occurs in exactly the same previously repigmented lesions, suggesting that autoimmune memory plays a role in the skin that is not cleared by current treatments [39]. Resident memory T (Trm) cells are a subset of long-lived T cells that persist within most nonlymphoid tissues after inflammation or infection driven by T cells [96, 97]. Trm cells of the skin are known of their long-term residence in the skin. They patrol their surroundings; the epidermis and papillary dermis, and rapidly respond when they encounter their cognate antigen [98]. They are defined by the cell surface expression of CD69, CD103, CD49a and CD44 [99]. As these cells are able to live in tissues for long time and rapidly evoke immunity reactions against viruses, they were strongly considered candidates for stimulating vitiligo lesional relapse [39]. Trm cells function has been the subject of debate. In some models, these cells sufficiently control viral titres during re-infection with no need for recirculating cells [100, 101]. In other contexts, they mainly synthesise cytokines for effector T cell recruitment from the circulation (Ariotti et al., 2014). However, CD8+ Trm cells are shown to have low cytotoxic potential.
In normal human skin CD8+ Trem cells demonstrated low levels of granzyme B and perforin [102]. Moreover, the effect of CD8+ Trem cells isolated from normal human skin on lysing allogenic target cells were significantly poorer than circulating effector memory T cells [103].Trm cells mediate the immune response to melanoma via inhibiting tumour outgrowth instead of tumour elimination, indicating that Trm cells lack cytotoxic ability [104]. Based on their low cytotoxic activity and efficient ability of producing cytokines, Trm cells may be involved in recruitment of effector cells from circulation [39]. In vitiligo mouse model, it was found that blockade of T cell migration to the skin or depletion of recirculating memory T cells reversed vitiligo, although the number of Trm cells was not affected [105]. It was therefore concluded that Trm cells cannot independently maintain vitiligo in the absence of recruitment of further T cells [105]. In this vitiligo mouse model, autoreactive melanocyte-specific CD8+ Trm cells were shown to synthesise IFN-γ and CXCL10, probably employing the IFN-γ-chemokine pathway to maintain vitiligo lesions [105]. Thus, Trm cells are likely to mediate the long-term maintenance and relapse of the disease in patients via cytokine-mediated recruitment of circulating T cells [39]. Notably, vitiligo patients with stable disease are considered to have continuing immune response, as evidenced the existence of Trm cells in vitiligo perilesional skin [69, 106]. These may be involved during a flare-up, as previously reported in psoriasis [107].