DECREASED INDUCIBLE EXPRESSION OF CD80 AND CD86 IN HUMAN MONOCYTES AFTER ULTRAVIOLET-B IRRADIATION - ITS INVOLVEMENT IN INACTIVATION OF ALLOGENECITY

Ultraviolet-B (UV-B) irradiation of antigen presenting cells (APCs) mo difies their allogenecity, resulting in inhibition of the proliferativ e response of T cells in mixed lymphocyte reaction (MLR). Costimulatio n by the CD28 ligand CD80 (B7/B7-1) and CD86 (B70/B7-2) plays an impor tant role during T-cell proliferation by augmenting synthesis of inter leukin-2 (IL-2) and other cytokines. In this study, we demonstrated in duced expression of both CD80 and CD86 during allogeneic MLR, though h uman freshly isolated monocytes express CD86 constitutively with a muc h lower level of CD80. A monoclonal antibody (MoAb) against CD86, but not CD80, efficiently inhibited allogeneic T-cell proliferative respon ses stimulated with highly purified monocytes. UV-B exposure (0 to 1,0 00 J/m(2)) of monocytes inhibited the proliferation of T lymphocytes i n MLR in a dose-dependent manner. Flow cytometric analysis showed that UV-B exposure of monocytes impaired the constitutive expression of CD 54 (intercellular adhesion molecule-1) by 24 hours after irradiation, but the effect on CD86 was relatively less. The surface expression of CD80, CD86, CD54, and HLA-DR on monocytes was further augmented by int erferon (IFN)-gamma; this cytokine-induced expression was dose-depende ntly reduced by UV-B irradiation. Similarly, the upregulation of these molecules following allogeneic MLR was downregulated by UV-B irradiat ion, UV-B irradiation of monocytes inhibited the expression of IL-2 mR NA in monocyte-stimulated allogeneic MLR. In contrast, the addition of anti-CD28 MoAb at the onset of MLR prevented, at least partially, the reduction of IL-2 mRNA. These results strongly suggest that the impai rment of inducible expression of CD86 and CD80 may contribute to the r educed MLR response following exposure of monocytes to UV-B. (C) 1996 by The American Society of Hematology.