Human epidermal cells synthesize HLA-DR alloantigens in vitro upon stimulation with gamma-interferon.
Under certain pathologic conditions, human keratinocytes synthesize and express HLA-DR antigens. Assuming that soluble mediators might be responsible for this phenomenon, differentiating, primarily DR-keratinocytes were grown in the presence or absence of mixed leukocyte culture supernatants and tested for Ia antigen expression. After 6 days of culture, keratinocytes displayed surface-bound HLA-DR alpha/beta complexes when exposed to mixed leukocyte culture supernatants but not when cultured in media alone. These HLA-DR moieties on keratinocytes result from active biosynthesis as evidenced by the demonstration of the intracytoplasmic HLA-DR gamma (invariant) chain within these cells. In view of reports that interferon-gamma promotes Ia-production in a variety of cell types, we reasoned that this lymphokine might be responsible for the Ia-inducing property of mixed lymphocyte culture supernatants. Indeed, recombinant interferon-gamma, but not interferon-alpha or interleukin-2, proved to be a potent stimulator of Ia expression by keratinocytes. The further finding that this event can be prevented by the addition of a monoclonal anti-interferon-gamma antibody strongly suggests that this cytokine is directly responsible for HLA-DR production by keratinocytes. The interferon-gamma-induced acquisition of HLA-DR antigens by primarily DR-keratinocytes may provide a useful tool to study the role of these alloantigens in T-cell activation and may also add to our understanding of mechanisms operative in epidermal cell-T-cell interactions.
Volc-Platzer
B
B
Leibl
H
H
Luger
T
T
Zahn
G
G
Stingl
G
G
D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D003470:Culture Media; D000078404:Epidermal Cells; D005455:Fluorescent Antibody Technique; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D012867:Skin / Q000276:immunology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D003470:Culture Media; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma