Bromberg J S, Chavin K D, Altevogt P, Kyewski B A, Guckel B, Naji A, Barker C F
Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia.
Transplantation. 1991 Jan;51(1):219-25. doi: 10.1097/00007890-199101000-00036.
The antimurine CD2 mAb 12-15 was administered intravenously to investigate the role of CD2 in cell-mediated immunity in vivo. The anti-CD2 mAb was able to diminish the contact sensitivity response to the hapten trinitrophenyl and was most effective when administered during the efferent or elicitative phase of immunity. Antibody treatment was also able to inhibit in vivo priming for subsequent generation of secondary, TNP-specific CTL in vitro. This inhibitory effect was most effective in the afferent or early phase of immunity. Indeed antibody could be injected at least 3 weeks prior to in vivo antigen priming, and the subsequent CTL response was still suppressed. Additional experiments showed a well-defined dose-response relationship between the amount of anti-CD2 administered and subsequent immunosuppression. Control experiments showed that other isotype-matched antibodies were not suppressive and that the anti-CD2 was not merely shifting the kinetics of the CTL response. Further experiments revealed that in vivo mAb treatment could also inhibit the subsequent development of primary, alloantigen-specific CTL in vitro while the mixed lymphocyte reaction (MLR) remained unchanged. FACS analysis revealed a marked downmodulation of CD2 in vivo, a small and variable decrease in CD8, and essentially no change in CD3 or CD4 after treatment with anti-CD2. The F(ab')2 fragment was not able to downmodulate CD2 or to suppress CTL activity at the doses tested. These results support a major role for CD2 in diverse aspects of cell-mediated immunity affecting both CD4+ and CD8+ effector T cells. The anti-CD2 mAb functions not by deleting or depleting relevant cell populations but rather by altering the array of cell surface receptors and subsequent responses to antigenic challenge.
静脉注射抗小鼠CD2单克隆抗体12 - 15，以研究CD2在体内细胞介导免疫中的作用。抗CD2单克隆抗体能够减弱对半抗原三硝基苯的接触敏感性反应，并且在免疫的传出或激发阶段给药时最为有效。抗体治疗还能够抑制体内引发，从而抑制随后在体外产生的继发性、TNP特异性细胞毒性T淋巴细胞（CTL）。这种抑制作用在免疫的传入或早期阶段最为有效。实际上，在体内抗原引发前至少3周注射抗体，随后的CTL反应仍会受到抑制。额外的实验表明，给予的抗CD2量与随后的免疫抑制之间存在明确的剂量反应关系。对照实验表明，其他同型匹配抗体没有抑制作用，并且抗CD2不仅仅是改变CTL反应的动力学。进一步的实验表明，体内单克隆抗体治疗还能够抑制体外原发性同种异体抗原特异性CTL的后续发育，而混合淋巴细胞反应（MLR）保持不变。流式细胞术分析显示，抗CD2治疗后，体内CD2明显下调，CD8有小幅度且可变的减少，而CD3或CD4基本没有变化。在测试剂量下，F(ab')2片段不能下调CD2或抑制CTL活性。这些结果支持CD2在影响CD4 +和CD8 +效应T细胞的细胞介导免疫的各个方面发挥主要作用。抗CD2单克隆抗体的作用不是通过删除或消耗相关细胞群体，而是通过改变细胞表面受体阵列以及随后对抗抗原攻击的反应来实现的。
