Chavin K D, Qin L, Yon R, Lin J, Yagita H, Bromberg J S
Department of Surgery, Medical University of South Carolina, Charleston 29425.
J Immunol. 1994 Apr 15;152(8):3729-39.
The mechanism by which anti-CD2 mAbs inhibit hapten-specific and alloantigen specific CTL was explored. In vivo administration of alpha-CD2 mAbs resulted in 80 to 100% inhibition of alloantigen specific CTLs. Mixing cells from control animals with cells from alpha-CD2-treated groups demonstrated transferable suppression of CTL (40-67% suppression). These suppressor cells were CD4+CD8- and associated with increased IL-4 and TGF-beta in culture as compared with controls. Anti-CD2 mAbs added at the initiation of culture resulted in 60 to 72% inhibition of trinitrophenyl-CTL, whereas mAbs added at the time of assay resulted in less than 50% inhibition of trinitrophenyl-CTLs. F(ab')2 and Fab alpha-CD2 produced inhibition similar to intact mAbs when added at the time of the lytic assay, whereas both produced only modest inhibition in vivo or when added at the initiation of culture. Alloantigen-specific CTLs were not affected by Ab addition to either culture or assay. The immunosuppressive effects were generalizable because a panel of alpha-CD2 mAbs were all comparably effective in suppressing hapten-specific CTLs when administered in vivo. The results demonstrate that the inhibitory effects are the result of blockade of receptor adhesion function during Ag priming or target recognition, Fc-related effects, and the generation of a negative regulatory, CD4+CD8-, IL-4- and TGF-beta-producing TH2 suppressor T cell.
对抗CD2单克隆抗体抑制半抗原特异性和同种异体抗原特异性细胞毒性T淋巴细胞（CTL）的机制进行了研究。体内给予α-CD2单克隆抗体可导致同种异体抗原特异性CTL受到80%至100%的抑制。将对照动物的细胞与α-CD2处理组的细胞混合，显示出CTL的可转移抑制作用（抑制率为40%-67%）。与对照组相比，这些抑制细胞为CD4+CD8-，且在培养中与白细胞介素-4（IL-4）和转化生长因子-β（TGF-β）的增加有关。在培养开始时添加抗CD2单克隆抗体可导致三硝基苯基特异性CTL受到60%至72%的抑制，而在检测时添加单克隆抗体则导致三硝基苯基特异性CTL受到的抑制小于50%。在溶细胞检测时添加F(ab')2和Fab α-CD2产生的抑制作用与完整单克隆抗体相似，而两者在体内或在培养开始时添加时仅产生适度抑制作用。向培养物或检测中添加抗体对同种异体抗原特异性CTL均无影响。免疫抑制作用具有普遍性，因为一组α-CD2单克隆抗体在体内给药时，在抑制半抗原特异性CTL方面均具有相当的效果。结果表明，抑制作用是由于在抗原致敏或靶标识别过程中受体黏附功能的阻断、Fc相关效应以及产生负调节性、CD4+CD8-、产生IL-4和TGF-β的辅助性T2抑制细胞所致。
