The mechanism of anti-CD3 monoclonal antibodies. Mediation of cytolysis by inter-T cell bridging.
The mechanism of anti-CD3 monoclonal antibodies. Mediation of cytolysis by inter-T cell bridging.
复制标题
抗CD3单克隆抗体的作用机制。
DOI：
10.1097/00007890-199010000-00030
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发表时间：
1990
期刊：
影响因子：
6.2
通讯作者：
Colvin,RB
中科院分区：
文献类型：
--
作者：
Wong,JT;Eylath,AA;Ghobrial,I;Colvin,RB
OKT 3是一种抗CD 3单克隆抗体，在体内消耗T细胞，是急性同种异体移植排斥反应最有效的抑制剂之一。这种抑制的机制尚不清楚。本研究调查抗CD 3抗体是否具有交联两种不同细胞上的CD 3并诱导T细胞之间的TCR依赖性抗体桥接细胞介导的细胞溶解（TCR-ABCMC）的能力。两种不同的抗-CD 3抗体（OKT 3和CD 3，3）和OKT 3 F（ab '）2都高度有效地诱导CD 8 + T细胞对CD 8+和CD 4 + T细胞的细胞溶解，以及诱导CD 4 + T细胞对CD 8 + T细胞的细胞溶解。单价0 KT 3 Fab的效力比0 KT 3 F（ab '）2低25-125倍。单价CD 3，X完全无效。细胞间桥接的必要性通过观察到抗-CD 3：抗-CD 4（CD 3，4）双特异性MAB（BSMAB）有效介导CD 4 + T细胞而不是CD 8 + T细胞被CD 8 + T细胞裂解而得到证明。这些研究表明，FcR介导的ADCC和补体结合对于二价抗CD 3 MAB裂解T细胞都不是必需的。T细胞间TCR-ABCMC可能在炎性组织中特别有效，例如排斥同种异体移植物和自身免疫性疾病，其中许多溶细胞性T淋巴细胞与其他T细胞密切相关。
OKT3, an anti-CD3 MAB, depletes T cells in vivo and is among the most potent inhibitors of acute allograft rejection. The mechanism of this inhibition is unknown. The present studies investigate whether anti-CD3 antibodies have the ability to crosslink CD3 on two different cells and induce TCR-dependent antibody-bridged cell-mediated cytolysis (TCR-ABCMC) between T cells. Two different anti-CD3 antibodies (OKT3 and CD3, 3) and OKT3 F (ab') 2 were all highly effective in inducing cytolysis of CD8+ and CD4+ T cells by CD8+ T cells, and CD8+ T cells by CD4+ T cells. Monovalent OKT3 Fab was 25–125-fold less potent than OKT3 F (ab') 2. Monovalent CD3, X was totally ineffective. The necessity for intercellular bridging was evidenced by the observation that an anti-CD3: anti-CD4 (CD3, 4) bispecific MAB (BSMAB) was effective in mediating lysis of CD4+ but not CD8+ T cells by CD8+ T cells. These studies indicate that neither FcR-mediated ADCC nor complement fixation is necessary for bivalent anti-CD3 MAB to lyse T cells. Inter-T cell TCR-ABCMC may be particularly effective in inflammatory tissues, such as rejecting allografts and autoimmune diseases, in which numerous cytolytic T lymphocytes are present in close association with other T cells.