02324nas a2200373 4500000000100000008004100001260001300042653001400055653001200069653002900081653002400110653002000134653001700154653002000171653002400191653001100215653002100226653001800247653002600265653000900291653002500300653001300325653002500338653003400363100001200397700001600409700001300425700001800438245010000456300001000556490000700566520136300573022001401936 1993 d c1993 Jan10a3T3 Cells10aAnimals10aAntigen-Presenting Cells10aAntigens, Bacterial10aCells, Cultured10aFormaldehyde10aHLA-DR Antigens10aHeat-Shock Proteins10aHumans10aInterferon-gamma10aKeratinocytes10aLymphocyte Activation10aMice10aMycobacterium leprae10aPolymers10aRecombinant Proteins10aT-Lymphocytes, Helper-Inducer1 aMutis T1 aDe Bueger M1 aBakker A1 aOttenhoff T H00aHLA class II+ human keratinocytes present Mycobacterium leprae antigens to CD4+ Th1-like cells. a43-510 v373 a

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, Th1-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-gamma, in an antigen-specific and HLA class II restricted manner. All T-cell clones tested also showed significant proliferation and IFN-gamma 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 1-like cells. It seems therefore possible that antigen presentation by KC contributes to the local cell-mediated immune responses in DTH lesions.

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