ACTIVATION OF HUMAN T-CELLS INVIVO FOLLOWING TREATMENT OF TRANSPLANT RECIPIENTS WITH OKT3

ACTIVATION OF HUMAN T-CELLS INVIVO FOLLOWING TREATMENT OF TRANSPLANT RECIPIENTS WITH OKT3
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DOI:
10.1097/00007890-199010000-00016
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发表时间:
1990-10-01
期刊:
影响因子:
6.2
通讯作者:
BLUESTONE, JA
BLUESTONE, JA
中科院分区:
医学2区
文献类型:
--
作者:
ELLENHORN, JDI;WOODLE, ES;BLUESTONE, JA

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在10名器官移植受者中在OKT 3施用之前和之后获得连续的淋巴结活检,以确定在OKT 3施用期间体内是否发生人T细胞的活化。在注射后2小时内,可以检测到OKT 3包被LN T细胞,并且在重组白细胞介素-2(rIL-2)存在下,LN T细胞也表现出体外增殖增强。白细胞介素-2受体(IL-2 R)在施用0 KT 3后48小时内在0 KT 3后LN T细胞上表达。此外,当置于混合淋巴细胞反应中时,后OKT 3 LN细胞也表现出增强的增殖。这是OKT 3在体内激活人类T细胞的第一个直接证明。这些数据支持T淋巴细胞活化和伴随的淋巴因子产生是与OKT 3治疗相关的副作用的原因的假设。免疫激活和抗供体MHC同种异体反应性的可能增强可能对临床器官移植中的抗CD 3和抗TCR单克隆抗体治疗以及癌症患者的免疫应答的增强具有重要意义。
Sequential lymph node biopsies were obtained prior to and following OKT3 administration in 10 organ transplant recipients to determine whether activation of human T cells occurs in vivo during OKT3 administration. Within 2 hr after injection, OKT3 can be detected coating LN T cells, and LN T cells also demonstrate enhanced proliferation in vitro in the presence of recombinant interleukin-2(rIL-2). Interleukin-2 receptor (IL-2R) is expressed on post-OKT3 LN T cells within 48 hr following administration of OKT3. In addition, when placed in a mixed lymphocyte reaction, post-OKT3 LN cells also demonstrate enhanced proliferation. This is the first direct demonstration of in vivo activation of human T cells by OKT3. These data support the hypothesis that T lymphocyte activation and concomitant production of lymphokines are responsible for the side effects associated with OKT3 treatment. Immune activation and possible enhancement of anti-donor MHC alloreactivity may have significant implications for anti-CD3 and anti-TCR monoclonal antibody therapy in clinical organ transplantation and for enhancement of the immune response in cancer patients.