HLA Class II⁺ Human Keratinocytes present Mycobacterium leprae Antigens to CD4⁺ Thl‐Like Cells

In a variety of inflammatory skin diseases like leprosy, keratinocytes (KC) are induced to express MHC class II molecules and may therefore serve as antigen‐presenting cells (APC) for MHC class II restricted T cells infiltrating the lesions. However, KC have been thought to be improper APC for MHC class II restricted T cells and to drive T cells into an anergic rather than into an activation state. We evaluated this issue in relation to leprosy and tested whether HLA‐DR⁺ KC could present M. leprae antigens to well‐defined, CD4 ⁺, cytotoxic as well as proliferative, Thl ‐like cell clones. Using a recently developed sensitive assay system which employs intact layers of basal KC as APC we found that most T‐cell clones (6/8) lysed HLA‐DR⁺ KC pulsed with M. leprae antigens. KC were only recognized after induction of HLA‐DR expression by IFN‐γ, in an antigen‐specific and HLA class II restricted manner. All T‐cell clones tested also showed significant proliferation and IFN‐γ production in response to M. leprae antigens presented by HLA‐DR⁺ KC, arguing against a KC dependent anergizing effect on T cells. Thus, HLA class II⁺ KC can function as proper APC for HLA class II restricted CD4⁺ Th l ‐like cells. It seems therefore possible that antigen presentation by KC contributes to the local cell‐mediated immune responses in DTH lesions.