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Accessory cell function of keratinocytes for superantigens. Dependence on lymphocyte function-associated
B J Nickoloff1, R S Mitra, J Green
1Department of Pathology, University of Michigan, Ann Arbor 48109-0755.
Journal of Immunology (Baltimore, Md. : 1950)
|March 15, 1993
Summary
Human skin cells, keratinocytes, can act as accessory cells to stimulate T cell proliferation in response to bacterial superantigens. The interaction between LFA-1 on T cells and ICAM-1 on keratinocytes is crucial for this immune response.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Epidermal keratinocytes are increasingly recognized for their active role in immune responses.
- T cell-mediated skin diseases like psoriasis and atopic dermatitis can be triggered by microbial infections.
Purpose of the Study:
- To investigate if human keratinocytes can provide costimulatory signals for T cell proliferation against bacterial superantigens.
- To elucidate the specific molecular interactions involved in keratinocyte-mediated T cell activation.
Main Methods:
- Human keratinocytes were treated with Interferon-gamma (IFN-γ) to induce expression of MHC class II (HLA-DR, HLA-DQ) and ICAM-1.
- T cell proliferation assays were performed using bacterial superantigens (staphylococcal enterotoxins A and B) in the presence of treated keratinocytes.
- Inhibition studies used monoclonal antibodies (mAbs) against LFA-1, ICAM-1, and CD28 ligands (BB-1, B7).
Main Results:
- IFN-γ-treated keratinocytes supported T cell proliferation induced by superantigens, PHA, and anti-CD3 mAb.
- The LFA-1/ICAM-1 interaction was identified as a major costimulatory pathway, with mAbs against LFA-1 or ICAM-1 significantly inhibiting superantigen-driven proliferation.
- Keratinocytes did not provoke an allogeneic T cell response, suggesting potential limitations in antigen presentation.
Conclusions:
- Keratinocytes function as accessory cells capable of supporting T cell proliferation via various stimuli.
- The LFA-1/ICAM-1 pathway is critical for keratinocyte-mediated costimulation in superantigen responses.
- The accessory function of keratinocytes may be relevant to the pathogenesis of skin immunologic disorders.