Puccetti P, Bianchi R, Romani L, Cenci E, Fioretti M C
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Int J Cancer. 1989 Feb 15;43(2):279-84. doi: 10.1002/ijc.2910430220.
Previous work has shown that murine lymphoma cells antigenically altered ("xenogenized") by drug treatment elicit strong in vivo resistance to the original cells. Moreover, splenocytes immune to a drug-treated variant (L5178Y/DTIC) of a murine lymphoma exert anti-parental tumor activity in an adoptive transfer system, an effect mediated by L3T4+ lymphocytes and associated with the detection of an anti-L5178Y delayed-type hypersensitivity (DTH) response. We now report that the in vivo activity of the tumor-immune L3T4+ lymphocytes is a radio-sensitive (2,500 rad in vitro) phenomenon that requires collaboration with radio-resistant, silica-sensitive syngeneic cells in the host, and is inhibited by treatment of recipient mice with monoclonal antibodies (MAbs) to the L3T4 antigen or murine interferon-gamma (IFN-gamma). In vitro, the tumor-immune L3T4+ lymphocytes produce interleukin 2 (IL-2), lymphotoxin (LT) and IFN-gamma activities on incubation with L5178Y cells and spleen-adherent cells. These results suggest that the mechanisms of anti-parental tumor protection by xenogenized cells involve specific induction of a DTH response mediated by the "inflammatory" (THI) subset of L3T4+ T lymphocytes and IFN-gamma activated macrophages.
先前的研究表明，经药物处理抗原性改变（“异种源化”）的鼠淋巴瘤细胞在体内对原始细胞产生强烈抗性。此外，对鼠淋巴瘤的药物处理变体（L5178Y/DTIC）免疫的脾细胞在过继转移系统中发挥抗亲代肿瘤活性，这种效应由L3T4 +淋巴细胞介导，并与抗L5178Y迟发型超敏反应（DTH）的检测相关。我们现在报告，肿瘤免疫的L3T4 +淋巴细胞的体内活性是一种放射敏感现象（体外2500拉德），需要与宿主中抗辐射、对二氧化硅敏感的同基因细胞协作，并且用针对L3T4抗原的单克隆抗体（MAb）或鼠γ干扰素（IFN-γ）处理受体小鼠可抑制该活性。在体外，肿瘤免疫的L3T4 +淋巴细胞与L5178Y细胞和脾黏附细胞孵育时产生白细胞介素2（IL-2）、淋巴毒素（LT）和IFN-γ活性。这些结果表明，异种源化细胞抗亲代肿瘤保护的机制涉及由L3T4 + T淋巴细胞的“炎性”（THI）亚群和IFN-γ激活的巨噬细胞介导的DTH反应的特异性诱导。
