FURTHER EVIDENCE FOR INVOLVEMENT OF BOTH CELL-MEDIATED AND HUMORAL IMMUNITY IN GENERALIZED VITILIGO

Immunohistochemical and immunoserological evidence supports the involv ement of both cell-mediated and humoral mechanisms in the pathogenesis of melanocyte destruction in vitiligo. Punch biopsies from depigmente d vitiliginous skin (VS), normal-looking pigmented skin (PS), and marg inal skin (MS) from patients with generalized vitiligo (n = 15) were l abeled with K 1.2.58, OKM1 (CD11b), Leu 11b (CD16), Leu 19 (CD56), IFN -gamma receptor, IL-2 receptor (CD25), IgG, IgM, C3c, and C3d MoAbs. I n addition, in vitro effects of vitiligo sera (n = 13) on human newbor n 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 fe w CD11b+ cells in the dermis and epidermis could be detected but no si gnificant numbers of CD16+ or CD56+ cells were seen among the mononucl ear cellular infiltrate. IL-2 and IFN-gamma receptors were clearly exp ressed by the cellular infiltrate. No significant deposition of comple ment or immunoglobulin was seen. The addition of vitiligo sera to HMel cultures induced a significant cellular proliferation. The stimulatio n of cell proliferation occurred regardless whether the sera were adde d alone or when preheated (56 degrees C for 1 hr) and then supplemente d 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, inc ubation of vitiligo sera together with normal lymphocytes with HMel si gnificantly decreased the number of living melanocytes in a dose depen dent manner, suggesting an antibody-dependent cellular cytotoxicity (A DCC) 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- an d IFN-gamma-receptor expression and the decrease in the number of livi ng cells by ADCC-like mechanisms provide further support for an autoim mune pathogenesis in vitiligo.