Renner C, Held G, Ohnesorge S, Bauer S, Gerlach K, Pfitzenmeier J P, Pfreundschuh M
Department of Hematology and Oncology, University of Saarland, Homburg/Saar, Germany.
Immunobiology. 1997 Jun;197(1):122-32. doi: 10.1016/S0171-2985(97)80062-9.
Bispecific monoclonal antibodies (Bi-mAb) with specificity for a tumor associated antigen and the CD3 or CD28 antigen on T lymphocytes, respectively, induce activation of resting T lymphocytes and target-specific tumor cell lysis. Former studies had confirmed that T cells expressing the CD45RO "memory" antigen at high levels were the most potent effectors of Bi-mAb-mediated cytotoxicity when compared to their "naive" counterparts expressing the CD45RA antigen. Further analysis of the T cell subpopulations revealed that within the memory T cell pool, CD8+ T cells were the effector cell, population with strongest cytolytic activity. The cytolytic activity was correlated with the expression level of perforin and granzymes B mRNA. Ca2+ complexing agents, which abrogate perforin activity, reduced necrosis, while inhibition of granzyme activity in effector or target-cells had a similar effect on apoptosis. These results confirm the crucial role perforin and granzymes play in target-cell lysis and explain why CD8+CD45RO+ T cells activated by combined CD3 and CD28 antigen triggering represent the T cell pool with highest cytolytic potential.
分别对肿瘤相关抗原以及T淋巴细胞上的CD3或CD28抗原有特异性的双特异性单克隆抗体（双特异性单抗）可诱导静息T淋巴细胞活化以及靶向特异性肿瘤细胞裂解。既往研究证实，与表达CD45RA抗原的“初始”对应细胞相比，高水平表达CD45RO“记忆”抗原的T细胞是双特异性单抗介导的细胞毒性作用中最有效的效应细胞。对T细胞亚群的进一步分析显示，在记忆T细胞库中，CD8⁺T细胞是具有最强溶细胞活性的效应细胞群体。溶细胞活性与穿孔素和颗粒酶B mRNA的表达水平相关。消除穿孔素活性的Ca²⁺络合剂可减少坏死，而效应细胞或靶细胞中颗粒酶活性的抑制对凋亡有类似作用。这些结果证实了穿孔素和颗粒酶在靶细胞裂解中所起的关键作用，并解释了为何通过联合CD3和CD28抗原触发而活化的CD8⁺CD45RO⁺T细胞代表了具有最高溶细胞潜力的T细胞库。
