Human keratinocyte-lymphocyte reactions in vitro

Area of Science:

• Immunology
• Dermatology
• Cell Biology

Background:

• Recombinant gamma interferon (r-IFN-gamma) is known to induce HLA-DR antigen synthesis and expression.
• Investigating the modulation and immunologic consequences of keratinocyte HLA-DR expression is crucial for understanding skin immunity.

Purpose of the Study:

• To explore how continuous versus pulse r-IFN-gamma dosage affects HLA-DR expression on keratinocytes.
• To determine the immunologic consequences of HLA-DR expression on keratinocytes in vitro.
• To elucidate the mechanisms underlying lymphocyte-keratinocyte interactions.

Main Methods:

• Keratinocyte cultures were treated with r-IFN-gamma under varying dosage conditions (continuous vs. pulse).
• HLA-DR expression levels were assessed, along with effects of trypsinization.
• Peripheral blood mononuclear leukocytes (PBMLs) were co-cultured with HLA-DR+ and HLA-DR- keratinocytes to evaluate immune responses.
• Inhibition of lectin-driven and mixed-lymphocyte reactions was measured.

Main Results:

• Continuous r-IFN-gamma dosage led to greater HLA-DR expression compared to pulse dosage.
• Trypsinization significantly decreased r-IFN-gamma-induced HLA-DR expression.
• Both HLA-DR+ and HLA-DR- keratinocytes induced RNA synthesis and gamma interferon production in PBMLs, indicating mononuclear cell activation.
• This activation did not result in significant mitogenesis, with only slightly increased [3H]thymidine incorporation observed.
• Cultured keratinocytes produced a soluble mediator that inhibited lectin-driven and mixed-lymphocyte reactions.

Conclusions:

• Keratinocyte HLA-DR expression is modulated by r-IFN-gamma dosage and cell preparation methods.
• Keratinocyte-derived soluble mediators can inhibit lymphocyte proliferation, suggesting a regulatory role in immune responses.
• Lymphocyte-keratinocyte interactions in vitro are complex, involving multiple cytokines, lymphokines, and prostaglandins.