ANALYSIS OF THE EFFECT OF CYTOKINES (INTERLEUKIN-2, INTERLEUKIN-3, INTERLEUKIN-4, AND INTERLEUKIN-6, GRANULOCYTE-MONOCYTE COLONY-STIMULATING FACTOR, AND INTERFERON-GAMMA) ON GENERATIONS OF PRIMARY CYTOTOXIC T-LYMPHOCYTES AGAINST A WEAKLY IMMUNOGENIC TUMOR
ANALYSIS OF THE EFFECT OF CYTOKINES (INTERLEUKIN-2, INTERLEUKIN-3, INTERLEUKIN-4, AND INTERLEUKIN-6, GRANULOCYTE-MONOCYTE COLONY-STIMULATING FACTOR, AND INTERFERON-GAMMA) ON GENERATIONS OF PRIMARY CYTOTOXIC T-LYMPHOCYTES AGAINST A WEAKLY IMMUNOGENIC TUMOR
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DOI：
10.1006/cimm.1995.1204
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发表时间：
1995-10-15
影响因子：
4.3
通讯作者：
LORD, EM
中科院分区：
文献类型：
--
作者：
MCADAM, AJ;PULASKI, BA;LORD, EM
我们已经研究了细胞因子（IL-2、IL-3、IL-4、IL-6、IFN-γ和GM-CSF）在单个肿瘤系统内产生原代细胞毒性T淋巴细胞（CTL）中的作用。用具有这些细胞因子的cDNA的表达载体转染鼠癌细胞系1。细胞系1表达低水平的I类MHC分子，但可以用二甲亚砜或IFN-γ诱导以表达高水平的I类MHC分子。I类低细胞系1细胞对CTL裂解不敏感，而I类高细胞系1被CTL裂解，这允许我们测定CTL活性。为了分离原代CTL，从体内生长的表达精氨酸的肿瘤或对照肿瘤中分离肿瘤浸润淋巴细胞。大多数细胞因子刺激非特异性杀伤细胞，但IL-2和IL-3刺激初级CTL。虽然单独的IFN-γ不产生初级CTL，但IFN-γ与IL-2的共表达导致CTL产生。这是首次比较一系列细胞因子对原代CTL发育的影响，对疫苗开发和免疫治疗具有重要意义。(C)出版社：Academic Press
We have investigated the role of cytokines (IL-2, IL-3, IL-4, IL-6, IFN-gamma, and GM-CSF) in the generation of primary cytotoxic T lymphocytes (CTL), within a single tumor system. The murine carcinoma line 1 was transfected with expression vectors with cDNA for these cytokines. Line 1 expresses low levels of class I MHC molecules, but can be induced with dimethyl sulfoxide or IFN-gamma to express high levels of class I. Class I low line 1 cells are not susceptible to CTL lysis, while class I high line 1 are lysed by CTL, which allows us to assay for CTL activity. To isolate primary CTL, tumor-infiltrating lymphocytes were isolated from cytokine-expressing or control tumors, growing in vivo. Most cytokines stimulated nonspecific killers, but IL-2 and IL-3 stimulated primary CTL. While IFN-gamma alone did not generate primary CTL, coexpression of IFN-gamma with IL-2 resulted in CTL generation. This is the first comparison of the effects of a series of cytokines on primary CTL development, and has important implications for vaccine development and immunotherapy. (C) 1995 Academic Press, Inc.