5-(3,3′-二甲基-1-三氮杂化)-咪唑-4-羧酰胺(DTIC)治疗小鼠淋巴瘤正常组织相容性抗原的体内表达

D. Taramelli , L. Romani , A. Bonmassar , A. Goldin , M.C. Fioretti
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引用次数: 7

摘要

在5-(3,3 ' -二甲基-1-三氮杂-)-咪唑-4-carboxamide (DTIC)治疗肿瘤宿主4-8代移植后,在Moloney病毒诱导的BALB/c来源的LSTRA淋巴瘤(H-2d)或化学诱导的DBA/2来源的L5178Y淋巴瘤中发现了新的移植抗原。通过对组织相容性小鼠的一次体内和二次体外致敏,发现dtic处理的LSTRA或L5178Y细胞系有明显的细胞介导的细胞毒性反应。此外,初步数据显示,在来自不同亲代淋巴瘤的dtic治疗亚群中,没有发现明显的抗原交叉反应性。为了测试DTIC细胞系是否能表达不同水平的正常组织相容性抗原,我们在体外生成针对H-2复合物或其亚区同种抗原的细胞毒淋巴细胞,并在短期51cr释放试验中检测对亲本或DTIC治疗的淋巴瘤的杀伤作用。用LSTRA或4个LSTRA/DTIC亚系进行冷抑制试验。结果显示,亲本和dtic处理的亚群在细胞毒性淋巴细胞识别的H-2抗原表达上几乎没有差异。此外,在L5178Y或L5178Y/DTIC淋巴瘤中未发现细胞毒性淋巴细胞检测到的H-2b或H-2k单倍型的外来H-2特异性。
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Expression of normal histocompatibility antigens in murine lymphomas treated with 5-(3,3′-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) in vivo

Novel transplantation antigens have been detected in a Moloney virus-induced LSTRA lymphoma of BALB/c origin (H-2d), or in a chemically-induced L5178Y lymphoma of DBA/2 origin, following treatment of tumor-bearing hosts with 5-(3,3′-dimethyl-1-triazeno-)-imidazole-4-carboxamide (DTIC), for 4–8 transplant generations. Marked cell-mediated cytotoxic responses against DTIC-treated LSTRA or L5178Y lines were found by primary in vivo and secondary in vitro sensitization of histocompatible mice. Moreover, preliminary data show that no obvious antigenic cross-reactivity can be found among DTIC-treated sublines derived from distinct parental lymphomas. To test whether DTIC lines would express variable levels of normal histocompatibility antigens, cytotoxic lymphocytes were generated in vitro against alloantigens of H-2 complex or sub-regions of it and tested against parental or DTIC-treated lymphomas in a short-term 51Cr-release assay. A cold-inhibition test was performed with LSTRA or 4 LSTRA/DTIC sublines. The results showed that little or no difference in the expression of H-2 antigens recognized by cytotoxic lymphocytes could be detected between parental and DTIC-treated sublines. Moreover, no foreign H-2 specificities of H-2b or H-2k haplotypes detectable by cytotoxic lymphocytes could have been found in L5178Y or L5178Y/DTIC lymphomas.

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