An immunohistological study of cutaneous lymphocytes in vitiligo

Abstract

In a study of 49 biopsies from the margins of depigmented cutaneous lesions in 18 patients with vitiligo, highly significant overall increases were found in CD3+, CD4+, and CD8+ T cells, though cell numbers in individual cases were often within the normal range. Many of the T cells were activated (MHC class II+, interferon gamma+), of CD45RO (UCHL1+) memory subset, and many expressed the cutaneous lymphocyte-associated antigen (HECA-452+) typical of skin-homing T cells. Immunohistologically, the most intense epidermal T-cell infiltration was present within 0.6 mm of the edge of the lesion in 10 of 13 double-stained sections with a clearly defined zone of melanocyte depletion. In 40 lesions from 17 patients seen 11-64 weeks after biopsy, no apparent association was found between T-cell numbers and disease activity as assessed by Köbnerization of biopsy wounds or spread of depigmentation. These findings are consistent with the hypothesis that lesional T cells rather than circulating antimelanocytic antibody may be responsible for the supposedly autoimmune but characteristically patchy destruction of cutaneous melanocytes in vitiligo. Nevertheless, many of the infiltrating T cells are probably innocent bystanders attracted by upregulated cell adhesion molecules near sites of melanocyte damage.

A Critical Appraisal of Vitiligo Etiologic Theories. Is Melanocyte Loss a Melanocytorrhagy?

“…A loss of melanocytes has been demonstrated in established vitiligo lesions (5,6). However, melanocyte destruction has never been clearly demonstrated in NSV.…”

Genes of the LMP/TAP cluster are associated with the human autoimmune disease vitiligo

“…12,13 Two principal hypotheses concerning the etiology of vitiligo include: (1) the self-destruct model, which suggests that biochemical and/or structural defects inherent to patient melanocytes contribute to the initiation and/or progression of melanocyte cytolysis; and (2) the autoimmune model, which suggests that melanocyte death occurs through inappropriate immune system destruction of pigment cells. 11,14 There is considerable evidence that disease progression in some vitiligo patients involves autoimmune attack of the melanocytes, as evidenced by the presence of both cellular [15][16][17] and humoral [18][19][20] antimelanocyte autoimmune responses.…”

Local Immune Response in Skin of Generalized Vitiligo Patients

“…Despite this evidence, the in situ data on the role of infiltrating immunocompetent cells in generalized vitiligenous lesions are limited (Abdel-Naser et al, 1994;Badri et al, 1993). We have previously reported that in inflammatory vitiligo, a rare type of depigmentary disease, skin infiltrates of T cells and macrophages around the perilesional (PL) site parallel the development of the lesions in a centrifugal manner (Le Poole et al, 1996).…”

“…We have previously reported that in inflammatory vitiligo, a rare type of depigmentary disease, skin infiltrates of T cells and macrophages around the perilesional (PL) site parallel the development of the lesions in a centrifugal manner (Le Poole et al, 1996). Although expression of CLA was evaluated in two studies, Badri et al (1993) and Le Poole et al (1996), the importance of CLA ϩ T cell subsets in relation to melanocyte destruction was not explicitly demonstrated by double-label immunohistochemistry. Subsequently, despite these reports, the extent to which local immune response is associated with the development of vitiligo is still debated (Berd et al, 1996), due to the lack of appropriate in vivo studies on the immunopathology of generalized vitiligo.…”