Local Immune Response in Skin of Generalized Vitiligo Patients

Abstract

SUMMARY:In situ immune infiltrates in lesional, perilesional, and nonlesional skin biopsies from patients with vitiligo were analyzed by immunohistochemistry and compared with immune infiltrates found in the skin of normal healthy donors and relevant disease controls. An increased influx of activated skin-homing T cells and macrophages were seen in the perilesional biopsies. The overall percentages of cutaneous leukocyte-associated antigen-positive (CLA ϩ ) T cells were similar to those found in normal healthy donors. This is compatible with the similar expression of E-selectin. Most strikingly, however, the CLA ϩ T cells in perilesional skin were mainly clustered in the vicinity of disappearing melanocytes, and 60% to 66% of these interacting T cells expressed perforin and granzyme-B. The perforin ϩ /granzyme-B ϩ cells were not seen in locations different from that of disappearing melanocytes. Interestingly, the majority of the infiltrating T cells were HLA-DR/CD8 ϩ . Another hallmark of the present study is the focal expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR in the epidermis at the site of interaction between the immune infiltrates and the disappearing melanocytes. The data presented in this study are consistent with a major role for skin-homing T cells in the death of melanocytes seen in vitiligo. (Lab Invest 2000, 80:1299-1309.

Association ofCYP2C9Genetic Variants with Vitiligo

“…An autoimmune process targeting melanocytes is considered to mediate its pathogenesis. Consistent with this hypothesis histological studies have reported the absence of melanocytes in the affected skin2. In addition to cellular immunity, multiple autoantibodies against melanocyte antigens including various enzymes and other substances have been detected in the sera of some patients with vitiligo3,4.…”

CXCL10 Is Critical for the Progression and Maintenance of Depigmentation in a Mouse Model of Vitiligo

“…T cells infiltrate the skin during vitiligo and localize to the epidermis where melanocytes, their target cells, reside. In lesional skin, CD8 + T cells are found in close proximity to dying melanocytes (15, 16), and one study reported that melanocyte-specific, CD8 + T cells isolated from lesional skin migrated into nonlesional skin ex vivo , found their melanocyte targets in situ , and killed them (13). The melanocyte niche in the basal layer of the epidermis is not vascularized, so T cells that migrate into the skin in vitiligo must efficiently navigate through the dermis to find their targets and mediate depigmentation.…”

Vitiligo - Part 1

“…87,88 It has been observed experimentally that in some patients with common vitiligo, there was infiltration of CLA + T cells in the perilesional skin, thus being possible that the recruitment of these T cells occurred through dendritic cells activation, and these in turn are activated at the epidermal trauma region. 89,90 Recently, data that may confirm this hypothesis were found, an immunohistochemistry study demonstrated an increased population of CD11c + myeloid dendritic dermal cells and CD207 + Langerhans cells in the lesional border of vitiligo patches. 91 …”