SPECIFIC CYTO-TOXICITY AGAINST AUTOLOGOUS TUMOR AND PROLIFERATIVE RESPONSES OF HUMAN-LYMPHOCYTES GROWN IN INTERLEUKIN-2
SPECIFIC CYTO-TOXICITY AGAINST AUTOLOGOUS TUMOR AND PROLIFERATIVE RESPONSES OF HUMAN-LYMPHOCYTES GROWN IN INTERLEUKIN-2
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DOI：
10.1002/ijc.2910290107
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发表时间：
1982-01-01
影响因子：
6.4
通讯作者：
BONNARD, GD
中科院分区：
文献类型：
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作者：
VOSE, BM;BONNARD, GD
采用淋巴细胞-肿瘤混合培养法(MLTC)体外致敏肿瘤患者的外周血淋巴细胞。在不连续的Percoll梯度上分离出原始细胞，结果显示[~3H]-胸腺嘧啶核苷掺入有明显的刺激作用。培养的T细胞(CTC)是通过在含有IL-2的条件培养液中生长而来的，并通过反复给予IL-2和在某些情况下添加辐照的同种异体血单个核细胞作为“填充物”来维持长达51天。这些培养物显示出对自体肿瘤的特异性细胞毒反应，仅在少数情况下对K562[人白血病]细胞有明显的自然杀伤(NK)。在预激淋巴细胞试验(PLT)中检测CTC对肿瘤的再刺激作用。在同一部位的自体肿瘤和同种异体肿瘤的组织学刺激下，[~3H]-胸腺嘧啶核苷摄取增加，但对非相关肿瘤或一组同种异体淋巴细胞无反应。在大多数病例中，再刺激或对单核细胞的细胞毒作用不能检测到对自体HLAD/DR的致敏作用。通过仔细选择MLTC的致敏原始细胞，可以获得具有辅助性(增殖性)和细胞毒性T细胞的CTC，并且这种CTC具有对肿瘤细胞的特异性反应。这些细胞试剂将有助于确定人类肿瘤的抗原性，并可能用于治疗。
Peripheral blood lymphocytes of cancer patients were sensitized in vitro to autologous tumor cells in mixed lymphocyte-tumor culture (MLTC). Blast cells were isolated on discontinuous Percoll gradients from MLTC which showed significant stimulation of [3H]-thymidine incorporation. Cultured T cells (CTC) were derived from these blasts by growth in conditioned medium containing interleukin-2 (IL-2) and maintained for up to 51 days by repeated feeding with IL-2 and in some cases by addition of irradiated allogeneic blood mononuclear cells as "fillers". These cultures showed specific cytotoxic reactivity against autologous tumor and in only a few cases was natural killing (NK) of K562 [human leukemia] cells apparent. Restimulation of CTC with tumor was measured in primed lymphocyte tests (PLT). Increased uptake of [3H]-thymidine was found upon stimulation by autologous tumor and allogeneic tumor of the same site and histology but there was no response to non-related tumors or to a panel of allogeneic lymphocytes. No sensitization to autologous HLA D/DR could be detected by restimulation or cytotoxicity against monocytes in the majority of cases. By careful selection of sensitized blasts from MLTC, it is possible to obtain CTC with helper (proliferative) and cytotoxic T cells and that such CTC have specific reactivity against tumor cells. These cellular reagents will be useful in defining the antigenicity of human neoplasms and possibly in therapy.