Fujihara M, Takahashi T A, Azuma M, Ogiso C, Maekawa T L, Yagita H, Okumura K, Sekiguchi S
Japanese Red Cross, Hokkaido Red Cross Blood Center, Sapporo, Japan.
Blood. 1996 Mar 15;87(6):2386-93.
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.
用紫外线B（UV-B）照射抗原呈递细胞（APC）可改变其同种异体性，导致混合淋巴细胞反应（MLR）中T细胞增殖反应受到抑制。CD28配体CD80（B7/B7-1）和CD86（B70/B7-2）的共刺激通过增强白细胞介素-2（IL-2）和其他细胞因子的合成，在T细胞增殖过程中发挥重要作用。在本研究中，我们证明了在同种异体MLR过程中CD80和CD86均有诱导表达，尽管人新鲜分离的单核细胞组成性表达CD86，而CD80的表达水平低得多。一种抗CD86单克隆抗体（MoAb），而非抗CD80单克隆抗体，能有效抑制用高度纯化单核细胞刺激的同种异体T细胞增殖反应。用UV-B（0至1000 J/m²）照射单核细胞以剂量依赖方式抑制MLR中T淋巴细胞的增殖。流式细胞术分析显示，照射后24小时，用UV-B照射单核细胞会损害CD54（细胞间黏附分子-1）的组成性表达，但对CD86的影响相对较小。干扰素（IFN）-γ可进一步增强单核细胞上CD80、CD86、CD54和HLA-DR的表面表达；UV-B照射可剂量依赖性降低这种细胞因子诱导的表达。同样，UV-B照射可下调同种异体MLR后这些分子的上调表达。用UV-B照射单核细胞可抑制单核细胞刺激的同种异体MLR中IL-2 mRNA的表达。相反，在MLR开始时加入抗CD28 MoAb可至少部分防止IL-2 mRNA的减少。这些结果强烈表明，CD86和CD80诱导表达的受损可能导致UV-B照射单核细胞后MLR反应降低。
