The Journal of Immunology, Vol 147, Issue 11 3794-3802, Copyright © 1991 by American Association of Immunologists

ARTICLES

Hyperstimulatory CD1a+CD1b+CD36+ Langerhans cells are responsible for increased autologous T lymphocyte reactivity to lesional epidermal cells of patients with atopic dermatitis

RS Taylor, O Baadsgaard, C Hammerberg and KD Cooper
Department of Dermatology, University of Michigan Medical School, Ann Arbor.

We studied whether abnormalities in epidermal APC could be responsible for intracutaneous T cell activation in atopic dermatitis (AD). In the absence of added Ag, patients' peripheral blood T cells demonstrated significantly increased proliferation to their autologous lesional epidermal cells (mean +/- SEM = 19,726 +/- 9,754 cpm [3H]TdR uptake) relative to epidermal cells from uninvolved AD skin (2179 +/- 697 cpm) (n = 10) (p = 0.0001, log transformed data). AD T cell proliferative responses to autologous epidermal cells were dependent upon cells expressing HLA-DR, CD1a, and CD36, and not upon keratinocytes or their cytokines. Ultrastructurally, these cells ranged from typical Langerhans cells to indeterminate cells with irregular nuclear contours. Enriched populations of lesional AD Langerhans cells were highly stimulatory for autologous T cells, whereas equal numbers of Langerhans cells from non atopic epidermis were poor stimulators, even at high concentrations. The dermal perivascular dendritic cell markers CD36 and CD1b, not usually present on normal epidermal APC, were expressed by 40 and 60% of lesional AD CD1a+ epidermal Langerhans cells, respectively. Addition of anti-CD1b to cocultures of AD epidermal cells and autologous T lymphocytes augmented T cell activation, suggesting that the expression of CD1b by AD Langerhans cells may represent over expression of a molecule functionally linked to the enhanced T cell stimulatory capacity of these cells. Thus, stimulatory signals for T cells contained within AD epidermis are carried by cells in an abnormal differentiation state as indicated by expression of phenotypic characteristics of both epidermal and dermal antigen presenting cells (HLA-DR+, CD1a+, CD1b+, CD36+). We propose that activation of autologous T cells by an altered cutaneous APC population may represent a mechanism for the hyperactive and disordered cell-mediated immune response that characterizes the dermatitic lesions of AD.

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