Further Evidence for Involvement of Both Cell Mediated and Humoral Immunity in Generalized Vitiligo

Immunohistochemical and immunoserological evidence supports the involvement of both cell‐mediated and humoral mechanisms in the pathogenesis of melanocyte destruction in vitiligo. Punch biopsies from depigmented vitiliginous skin (VS), normal‐looking pigmented skin (PS), and marginal skin (MS) from patients with generalized vitiligo (n = 15) were labeled with K 1.2.58, OKM1 (CD11b), Leu 11b (CD16), Leu 19 (CD56), IFN‐γreceptor, IL‐2 receptor (CD25), IgG, IgM, C3c, and C3d MoAbs. In addition, in vitro effects of vitiligo sera (n = 13) on human newborn melanocytes (HMel) under different culture conditions were studied. The immunohistochemical findings showed absence of K 1.2.58+ epidermal melanocytes in VS and abnormal morphology in MS. In these areas, a few CD11b + cells in the dermis and epidermis could be detected but no significant numbers of CD16+ or CD56+ cells were seen among the mononuclear cellular infiltrate. IL‐2 and IFN‐γ receptors were clearly expressed by the cellular infiltrate. No significant deposition of complement or immunoglobulin was seen. The addition of vitiligo sera to HMel cultures induced a significant cellular proliferation. The stimulation of cell proliferation occurred regardless whether the sera were added alone or when preheated (56°C for 1 hr) and then supplemented with a complement source (P < 0.01 at 2%, P < 0.001 at 10%, and P < 0.01 at 20% for sera alone) (P > 0.05 at 2%, P < 0.05 at 10%, and P < 0.01 at 20% for decomplemented sera plus complement). In contrast, incubation of vitiligo sera together with normal lymphocytes with HMel significantly decreased the number of living melanocytes in a dose dependent manner, suggesting an antibody‐dependent cellular cytotoxicity (ADCC) reaction (P < 0.01 at 2% and 10%, P < 0.001 at 20%). The presence of lymphocytic infiltrate at marginal skin with evidence for IL‐2‐ and IFN‐γ‐receptor expression and the decrease in the number of living cells by ADCC‐like mechanisms provide further support for an autoimmune pathogenesis in vitiligo.