Overexpression of CD1d by keratinocytes in psoriasis and CD1d-dependent IFN-gamma production by NK-T cells

The MHC class I-like protein CD1d is a nonpolymorphic molecule that plays a central role in development and activation of a subset of T cells that coe xpress receptors used by NK cells (NK-T cells). Recently, T cells bearing N K receptors were identified in acute and chronic lesions of psoriasis, To d etermine whether NK-T cells could interact with epidermal cells, we examine d the pattern of expression of CD1d in normal skin, psoriasis, and related skin disorders, using a panel of CD1d-specific mAbs, CD1d was expressed by keratinocytes in normal skin, although expression was at a relatively low l evel and was generally confined to upper level keratinocytes immediately be neath the lipid-rich stratum corneum. In contrast, there was overexpression of CD1d in chronic, active psoriatic plaques. CD1d could be rapidly induce d on keratinocytes in normal skin by physical trauma that disrupted barrier function or by application of a potent contact-sensitizing agent. Keratino cytes displayed enhanced CD1d following exposure to IFN-gamma, Combining CD 1d-positive keratinocytes with human NK-T cell clones resulted in clusterin g of NK-T cells, and while no significant proliferation ensued, NK-T cells became activated to produce large amounts of IFN-gamma. We conclude that CD 1d can be expressed in a functionally active form by keratinocytes and is u p-regulated in psoriasis and other inflammatory dermatoses. The ability of IFN-gamma to enhance keratinocyte CD1d expression and the subsequent abilit y of CD1d-positive keratinocytes to activate NK-T cells to produce IFN-gamm a, could provide a mechanism that contributes to the pathogenesis of psoria sis and other skin disorders.