Bianchi R, Fioretti M C, Grohmann U, Binaglia L, Romani L, Puccetti P
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Int J Immunopharmacol. 1992 Jul;14(5):915-21. doi: 10.1016/0192-0561(92)90091-x.
We have investigated the tumor-specific reactivity of different T-cell subsets from mice primed with clonal variants of L5178Y and P815 cells treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In both tumor systems, anti-parental tumor immunity and protection against non-immunogenic clones were only induced by vaccinating the hosts with highly immunogenic cell variants, and the effect correlated with the detection of TATA-specific delayed-type hypersensitivity (DTH) reactions. The footpad reaction was transferable with spleen cell populations from immunized mice, and enrichment of splenic lymphocytes in L3T4+ but not Lyt-2+ lymphocytes increased the footpad swelling. Unfractionated spleen cell populations from immunized mice released high amounts of IL-2 and IFN-gamma in vitro in response to parental antigens. Purified L3T4+ and Lyt-2+ lymphocytes also produced IFN-gamma when incubated in vitro with the parental tumors and accessory cells. It is suggested that the mechanisms of anti-parental tumor immunity induced by MNNG-treated variants may be similar to those described previously for triazene-xenogenized L5178Y/DTIC cells, and may involve induction of a tumor-specific DTH reaction and IFN-gamma-mediated stimulation of non-specific tumoricidal effects.
我们研究了用经N-甲基-N'-硝基-N-亚硝基胍(MNNG)处理的L5178Y和P815细胞的克隆变体免疫的小鼠中不同T细胞亚群的肿瘤特异性反应性。在这两种肿瘤系统中,只有用高度免疫原性的细胞变体接种宿主才能诱导抗亲本肿瘤免疫和针对非免疫原性克隆的保护作用,并且这种效应与检测到TATA特异性迟发型超敏反应(DTH)相关。足垫反应可通过免疫小鼠的脾细胞群体转移,并且L3T4 +而非Lyt-2 +淋巴细胞在脾淋巴细胞中的富集增加了足垫肿胀。免疫小鼠的未分离脾细胞群体在体外对亲本抗原产生大量的IL-2和IFN-γ。纯化的L3T4 +和Lyt-2 +淋巴细胞在体外与亲本肿瘤和辅助细胞一起孵育时也产生IFN-γ。提示MNNG处理的变体诱导的抗亲本肿瘤免疫机制可能与先前描述的三氮烯-异种源化L5178Y / DTIC细胞的机制相似,并且可能涉及诱导肿瘤特异性DTH反应和IFN-γ介导的非特异性杀肿瘤作用的刺激。