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) modifies their allogenecity, resulting in inhibition of the proliferative response of T cells in mixed lymphocyte reaction (MLR). Costimulation by the CD28 ligand CD80 (B7/B7-1) and CD86 (B70/B7-2) plays an important role during T-cell proliferation by augmenting synthesis of interleukin-2 (IL-2) and other cytokines. In this study, we demonstrated induced expression of both CD80 and CD86 during allogeneic MLR, though human freshly isolated monocytes express CD86 constitutively with a much lower level of CD80. A monoclonal antibody (MoAb) against CD86, but not CD80, efficiently inhibited allogeneic T-cell proliferative responses stimulated with highly purified monocytes. UV-B exposure (0 to 1,000 J/m2) of monocytes inhibited the proliferation of T lymphocytes in MLR in a dose-dependent manner. Flow cytometric analysis showed that UV-B exposure of monocytes impaired the constitutive expression of CD54 (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 interferon (IFN)-gamma; this cytokine-induced expression was dose-dependently reduced by UV-B irradiation. Similarly, the upregulation of these molecules following allogeneic MLR was downregulated by UV-B irradiation. UV-B irradiation of monocytes inhibited the expression of IL-2 mRNA 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 impairment of inducible expression of CD86 and CD80 may contribute to the reduced MLR response following exposure of monocytes of UV-B.
Fujihara
M
M
Japanese Red Cross, Hokkaido Red Cross Blood Center, Sapporo, Japan.
Takahashi
T A
TA
Azuma
M
M
Ogiso
C
C
Maekawa
T L
TL
Yagita
H
H
Okumura
K
K
Sekiguchi
S
S
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen; D001483:Base Sequence; D004307:Dose-Response Relationship, Radiation; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006684:HLA-DR Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation / Q000528:radiation effects*; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014466:Ultraviolet Rays
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma