HLA class II+ human keratinocytes present Mycobacterium leprae antigens to CD4+ Th1-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, 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.
Mutis
T
T
Department of Immunohaematology, University Hospital Leiden, The Netherlands.
De Bueger
M
M
Bakker
A
A
Ottenhoff
T H
TH
D016475:3T3 Cells; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D005557:Formaldehyde / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000032:analysis*; D006360:Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D015603:Keratinocytes / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D009166:Mycobacterium leprae / Q000276:immunology*; D011108:Polymers / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000942:Antigens, Bacterial; D006684:HLA-DR Antigens; D006360:Heat-Shock Proteins; D011108:Polymers; D011994:Recombinant Proteins; D005557:Formaldehyde; D007371:Interferon-gamma; C003043:paraform