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HLA class II+ human keratinocytes present Mycobacterium leprae antigens to CD4+ Th1-like cells
T Mutis1, M De Bueger, A Bakker
1Department of Immunohaematology, University Hospital Leiden, The Netherlands.
Insights
In leprosy, keratinocytes (KC) present Mycobacterium leprae antigens to T cells, activating them. This challenges the idea that KC induce T-cell anergy, suggesting KC play a role in skin immunity.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Keratinocytes (KC) in inflammatory skin diseases express MHC class II molecules, suggesting antigen-presenting cell (APC) roles.
- However, KC were previously thought to induce T-cell anergy rather than activation.
Purpose of the Study:
- To evaluate if HLA-DR+ KC can properly present Mycobacterium leprae antigens to CD4+ T cells in leprosy.
- To determine if KC induce T-cell anergy or activation in this context.
Main Methods:
- Utilized a sensitive assay with intact basal KC layers as APC.
- Tested antigen presentation of M. leprae antigens to well-defined, CD4+, Th1-like T-cell clones.
Main Results:
- Most T-cell clones (6/8) lysed HLA-DR+ KC pulsed with M. leprae antigens.
- KC were recognized in an antigen-specific and HLA class II-restricted manner after IFN-gamma induction.
- All T-cell clones showed proliferation and IFN-gamma production, indicating activation, not anergy.
Conclusions:
- HLA class II+ KC function as effective APC for HLA class II-restricted CD4+ Th1-like cells.
- Antigen presentation by KC likely contributes to local cell-mediated immune responses in delayed-type hypersensitivity (DTH) lesions.
Abstract:
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.