Epidermal cell-contra-interleukin 1 inhibits human accessory cell function by specifically blocking interleukin 1 activity.
Ultraviolet B (UVB) radiation (280-320 nm) is capable of suppressing selected cell mediated immune responses by inhibiting the function of antigen presenting/accessory cells. Human keratinocytes and carcinoma cell lines (A431) upon UVB radiation or treatment with PMA secrete a suppressor factor, which blocks IL 1 activity (hEC-contra-IL 1). Therefore, the capacity of this UVB-inducible cytokine to modulate human accessory cell function was tested. Human peripheral blood mononuclear cells were stimulated with the mitogenic anti-CD3 monoclonal antibody OKT3 and thymidine incorporation into proliferating T-cells was measured as an index for monocyte accessory cell activity. Addition of hEC-contra-IL 1 which was purified by HPLC chromatography partially decreased OKT3 induced T-cell proliferation in a dose dependent manner. Human EC-contra-IL 1, however, failed to inhibit blastogenesis when T-cells depleted of accessory cells were stimulated in an accessory cell independent fashion via OKT3 attached to the bottom of microtiter plates. Recombinant human (rh) IL 1, but not rhIL 6 was able to reconstitute hEC-contra-IL 1 suppressed blastogenesis in a dose dependent manner. Furthermore, the combined addition of h-EC-contra-IL 1 and an antibody against rhIL 6 to cultures resulted in an additive inhibitory effect which could not be observed when hEC-contra-IL 1 was added together with a monoclonal antibody against rhIL 1 alpha/beta. These studies indicate that hEC-contra-IL 1 is capable of suppressing human accessory cell function by specifically blocking IL 1 activity. This property of hEC-contra-IL 1 points to a novel mechanism by which UVB radiation may modulate human accessory cell function in an indirect manner.
Krutmann
J
J
Department of Dermatology II, University of Vienna, Austria.
Schwarz
T
T
Kirnbauer
R
R
Urbanski
A
A
Luger
T A
TA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D015603:Keratinocytes / Q000276:immunology / Q000528:radiation effects; D008213:Lymphocyte Activation; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins