Mukherji B, Wilhelm S A, Guha A, Ergin M T
J Immunol. 1986 Mar 1;136(5):1888-92.
The potential existence of down-regulation of cytotoxic immune response against an autologous human melanoma line was investigated as a possible explanation for cytotoxic unresponsiveness against the autologous melanoma cells. The melanoma cell line, PJ-M, was established and lymph node resident lymphocytes (LNL) were isolated from a lymph node which was partially infiltrated with the melanoma cells. Autologous peripheral blood lymphocytes (PBL) were sensitized in in vitro co-culture (IVC) against radiated PJ-M cells in the presence or absence of PJ-M-sensitized LNL and enriched suppressor (OKT8+) or inducer (OKT4+) LNL populations, and were assayed for cytotoxicity in a 4-hr 51Cr-release microcytotoxicity assay. Significant cytotoxic response against PJ-M could be generated in the PBL, but not in the LNL. The addition of sensitized, unfractionated LNL, OKT8+, or OKT4+ LNL populations abrogated cytotoxic response in the PBL against PJ-M. The suppression of cytotoxic response was induced selectively against the PJ-M targets, because IVC of PBL in the presence of the sensitized LNL did not affect the generation of polyclonal cytotoxic alloreactivities, nor did they abrogate the generation of cytotoxic response against allogeneic targets in IVC against the corresponding allogeneic targets. These results suggest the possibility that cytotoxic immune response against the autologous melanoma cells might have been suppressed by the individual's own immunoregulatory circuit.
针对自体人黑色素瘤细胞系的细胞毒性免疫反应下调的潜在存在情况进行了研究,以此作为对自体黑色素瘤细胞细胞毒性无反应性的一种可能解释。建立了黑色素瘤细胞系PJ-M,并从部分被黑色素瘤细胞浸润的淋巴结中分离出淋巴结驻留淋巴细胞(LNL)。在有或无PJ-M致敏的LNL以及富集的抑制性(OKT8 +)或诱导性(OKT4 +)LNL群体存在的情况下,将自体外周血淋巴细胞(PBL)在体外共培养(IVC)中对经辐射的PJ-M细胞进行致敏,并在4小时的51Cr释放微量细胞毒性试验中检测其细胞毒性。PBL中可产生针对PJ-M的显著细胞毒性反应,但LNL中则不能。添加致敏的、未分级的LNL、OKT8 +或OKT4 + LNL群体可消除PBL对PJ-M的细胞毒性反应。细胞毒性反应的抑制是针对PJ-M靶标选择性诱导的,因为在致敏LNL存在的情况下PBL的IVC不影响多克隆细胞毒性同种异体反应性的产生,也不会消除IVC中针对相应同种异体靶标的对同种异体靶标的细胞毒性反应的产生。这些结果提示,针对自体黑色素瘤细胞的细胞毒性免疫反应可能已被个体自身的免疫调节回路所抑制。