Sido B, Dengler T J, Otto G, Zimmermann R, Müller P, Meuer S C
Department of Surgery, University of Heidelberg, Germany.
Eur J Immunol. 1998 Apr;28(4):1347-57. doi: 10.1002/(SICI)1521-4141(199804)28:04<1347::AID-IMMU1347>3.0.CO;2-L.
CD2 is a co-stimulatory receptor involved in T cell activation. Here we report on immunosuppressive effects of three mouse CD2 monoclonal antibodies (OX34, OX54, OX55) directed against non-overlapping epitopes of the rat CD2 receptor on various modes of T cell activation in vitro and in vivo. Although non-ligand-blocking OX54 and OX55, in concert, activated T cells through CD2 in vitro, they individually suppressed the mixed lymphocyte reaction (MLR) and significantly prolonged allograft survival after rat heart transplantation in vivo. Phenotype analysis revealed that OX55 significantly down-modulated CD2 in vivo, whereas OX54 depleted T cells. Graft rejection coincided with re-expression of CD2 and clearance of OX55 from serum, whereas T cell depletion by OX54 outlasted the period of graft survival. The most suppressive antibody, OX34, down-modulated CD2 and inhibited T cell activation through the TCR or CD2 and the MLR and prolonged median allograft survival time from 7 days in controls to 45 days in the absence of any additional treatment. Graft survival was clearly dose dependent and correlated with the duration of CD2 down-modulation and the presence of circulating CD2 antibody in serum. Importantly, the specific antibody production to a T cell-dependent antigen as demonstrated by immunization with keyhole limpet hemocyanin in vivo remained unaffected after treatment with OX34. These results demonstrate the pivotal role of CD2 signaling in mediating allogeneic immune reactions after vascularized organ transplantation while allowing specific humoral immune responses in vivo.
CD2是一种参与T细胞活化的共刺激受体。在此，我们报告了三种针对大鼠CD2受体非重叠表位的小鼠CD2单克隆抗体（OX34、OX54、OX55）在体外和体内对各种T细胞活化模式的免疫抑制作用。尽管非配体阻断性的OX54和OX55在体外可通过CD2共同激活T细胞，但它们各自均可抑制混合淋巴细胞反应（MLR），并在体内大鼠心脏移植后显著延长同种异体移植物的存活时间。表型分析显示，OX55在体内可显著下调CD2，而OX54可使T细胞耗竭。移植物排斥反应与CD2的重新表达以及血清中OX55的清除同时发生，而OX54导致的T细胞耗竭持续时间超过移植物存活期。抑制作用最强的抗体OX34可下调CD2，并通过TCR或CD2抑制T细胞活化以及MLR，使同种异体移植物的中位存活时间从对照组的7天延长至未进行任何额外治疗时的45天。移植物存活明显呈剂量依赖性，且与CD2下调的持续时间以及血清中循环CD2抗体的存在相关。重要的是，在用OX34治疗后，体内用钥孔戚血蓝蛋白免疫所证明的针对T细胞依赖性抗原的特异性抗体产生未受影响。这些结果表明，CD2信号在介导血管化器官移植后的同种异体免疫反应中起关键作用，同时在体内允许特异性体液免疫反应。
