Independent cell types are involved in the induction of antimelanoma responses in C57BL/6 mice immunized with interleukin-2-secreting allogeneic mouse fibroblasts expressing melanoma-associated antigens.
Independent cell types are involved in the induction of antimelanoma responses in C57BL/6 mice immunized with interleukin-2-secreting allogeneic mouse fibroblasts expressing melanoma-associated antigens.
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在用表达黑色素瘤相关抗原的分泌白细胞介素 2 的同种异体小鼠成纤维细胞免疫的 C57BL/6 小鼠中，独立的细胞类型参与诱导抗黑色素瘤反应。
DOI：
10.1097/00002371-199311000-00008
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Cohen,EP
中科院分区：
文献类型：
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作者：
Kim,TS;Collins,MK;Cohen,EP
在将来自初始C57 BL/6小鼠（H-2 B）的脾细胞与经遗传修饰以表达黑素瘤相关抗原（MAA）并分泌白细胞介素（IL）-2（RLBA-IL-2细胞）的LM小鼠成纤维细胞（H-2 k）共孵育期间，产生了细胞抗黑素瘤免疫应答。将来自未处理小鼠的脾细胞与表达MAA但不分泌IL-2的同种异体细胞（H-2 k）（RLBA-ZipNeo细胞）或分泌IL-2但不形成MAA的同种异体细胞（H-2 k）（LM-IL-2细胞）共孵育后，也产生了抗黑色素瘤应答。然而，在这些情况下，应答的幅度显著小于（p< 0.01）随后脾细胞与将IL-2分泌与MAA表达相结合的同种异体细胞构建体（RLBA-IL-2）共孵育。LM（TK-）细胞（H-2 k）或B16细胞（H-2 B）未能在C57 BL/6小鼠的脾细胞群中产生抗黑色素瘤免疫反应。通过在加入细胞免疫原之前用单克隆抗体预先耗竭T细胞亚群，确定了由遗传修饰细胞诱导抗黑色素瘤应答所涉及的细胞类型。如果细胞免疫原不分泌IL-2（RLBA-ZipNeo细胞），则在T辅助细胞耗竭的脾细胞群中不能产生抗黑色素瘤应答。在与经修饰以分泌IL-2的构建体（RLBA-IL-2或LMIL-2）共孵育的细胞群中，先前T辅助细胞的耗竭不影响抗黑素瘤应答的诱导。巨噬细胞在诱导抗黑色素瘤反应中的作用通过巨噬细胞耗尽的群体在与IL-2分泌或非分泌细胞构建体共孵育后未能产生反应来指示。
Cellular antimelanoma immune responses developed during the coincubation of spleen cells from naive C57BL/6 mice (H-2 b) with LM mouse fibroblasts (H-2 k) genetically modified to express melanoma-associated antigens (MAA) and to secrete interleukin (IL)-2 (RLBA-IL-2 cells). Antimelanoma responses also developed following coincubation of spleen cells from naive mice with allogeneic cells (H-2 k) that expressed MAA, but did not secrete IL-2 (RLBA-ZipNeo cells), or allogeneic cells (H-2 k) that secreted IL-2, but did not form MAA (LM-IL-2 cells). However, in these instances, the magnitude of the responses was significantly less (p< 0.01) than followed coincubation of spleen cells with the allogeneic cell construct (RLBA-IL-2) that combined IL-2 secretion with the expression of MAA. LM (TK-) cells (H-2 k) or B16 cells (H-2 b) failed to generate antimelanoma immune responses in populations of spleen cells from C57BL/6 mice. The cell types involved in the induction of the antimelanoma response by the genetically modified cells were determined by prior depletion of T-cell subsets with monoclonal antibodies before the addition of the cellular immunogens. Antimelanoma responses failed to develop in spleen cell populations depleted of T-helper cells if the cellular immunogen was non-IL-2 secreting (RLBA-ZipNeo cells). Prior depletion of T-helper cells did not affect the induction of an antimelanoma response in cell populations coincubated with constructs (RLBA-IL-2 or LMIL-2) modified to secrete IL-2. The role of macrophages in the induction of the antimelanoma response was indicated by failure of macrophage-depleted populations to develop responses following coincubation with IL-2-secreting or nonsecreting cell constructs.