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Human keratinocytes activate primed major and minor histocompatibility antigen specific Th cells in vitro
M de Bueger1, A Bakker, E Goulmy
1Department of Immunohaematology, University Hospital, Leiden, The Netherlands.
Insights
Activated keratinocytes can stimulate T cells, influencing skin immunity. Specific conditions, like cell adherence, are crucial for this interaction, potentially enhancing immune responses.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Keratinocytes express MHC class II and ICAM-1 during skin inflammation.
- The role of keratinocyte-T cell interactions in cutaneous immunity is debated.
- Understanding these interactions is key to modulating inflammatory skin conditions.
Purpose of the Study:
- To investigate if interferon-gamma (IFN-γ) stimulated keratinocytes activate T helper (Th) cell clones in vitro.
- To determine the factors influencing keratinocyte-mediated T cell activation.
- To explore the implications for cutaneous immune responses.
Main Methods:
- Co-culture of IFN-γ stimulated human keratinocytes with established Th cell clones.
- Analysis of T cell proliferation in response to intact keratinocyte layers versus keratinocytes in suspension.
- Comparison of keratinocyte activating potential with professional antigen-presenting cells (APCs).
Main Results:
- Keratinocytes activated allo-MHC and minor histocompatibility (mH) antigen-specific Th cell clones in a HLA-DR and LFA-1/ICAM-1 dependent manner.
- Activation was observed with adherent keratinocytes at low densities, but not with keratinocytes in suspension.
- Keratinocyte T cell activating potential was lower than professional APCs like peripheral blood mononuclear cells (PMNCs) and EBV-B lymphoblastoid cell lines (LCLs).
Conclusions:
- In vitro conditions significantly impact the observed T cell activating potential of MHC class II-expressing keratinocytes.
- Activated keratinocytes can enhance, not just tolerate, cutaneous immune responses.
- These findings suggest a dual role for keratinocyte-T cell interactions in skin immunity.
Abstract:
Keratinocytes are activated to express MHC class II and ICAM-1 molecules during cutaneous inflammatory reactions. It is controversial how the interaction between these 'nonprofessional' antigen presenting cells (APC) and infiltrating T cells affects the local inflammatory response. To address this issue we analyzed whether IFN gamma-treated cultured human keratinocytes would activate established Th cell clones in vitro. Three allo DR specific T cell clones were induced to proliferate in a HLA-DR and LFA-1/ICAM-1 dependent fashion upon coculture with intact layers of IFN gamma stimulated keratinocytes. Likewise, keratinocytes also could activate two out of four minor histocompatibility (mH) antigen specific Th cell clones obtained from peripheral blood leukocytes (PBL) of graft versus host disease patients. The T cell activating potential of MHC class II+ keratinocytes was shown to be relatively low compared to specialized APC as PMNC and EBV-BLCL. Most strikingly, measurable allo MHC and mH antigen specific Th cell proliferation was only induced by using adherent keratinocytes at low cell densities, but not by keratinocytes in suspension. The results presented here indicate that in vitro conditions may crucially influence observations regarding the T cell activating potential of MHC class II expressing keratinocytes. Furthermore, our results indicate that, in addition to a tolerizing effect as suggested by previous reports, interaction of primed antigen specific T cells with activated keratinocytes may also result in enhancement of a cutaneous immune response in vivo.