CD8+ T cell concentration determines their efficiency in killing cognate antigen-expressing syngeneic mammalian cells in vitro and in mouse tissues.
CD8+ T cell concentration determines their efficiency in killing cognate antigen-expressing syngeneic mammalian cells in vitro and in mouse tissues.
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DOI：
10.1084/jem.20091279
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发表时间：
2010-01-18
期刊：
影响因子：
--
通讯作者：
Silverstein SC
中科院分区：
文献类型：
--
作者：
Budhu S;Loike JD;Pandolfi A;Han S;Catalano G;Constantinescu A;Clynes R;Silverstein SC
我们描述了一个定量模型，用于评估抗原特异性CD8+T细胞在体外和体内的杀伤活性，其中抗原特异性CD8+T细胞的浓度决定了这些细胞在体外和体内杀死包装细胞颗粒、三维胶原纤维蛋白凝胶和已建立的黑色素瘤中表达同源抗原的黑色素瘤细胞的效率。与黑色素瘤细胞克隆形成试验相结合，胶原-纤维蛋白凝胶的灵敏度是通常用于测量CD8+T细胞杀伤活性的包装细胞球类型的4,500-5,500倍。以前用来描述中性粒细胞在体外和体内杀菌活性的方程也描述了抗原特异性CD8+T细胞介导的表达同源抗原的黑色素瘤细胞在胶原-纤维蛋白凝胶中的体外和体内移植瘤中的细胞溶解。我们使用这个方程来计算抗原特异的CD8+T细胞的临界浓度，这是这些细胞保持恒定的浓度所需的浓度，而这些细胞的浓度与不断增长的表达同源抗原的黑色素瘤细胞的浓度相同。已发表的体外过继转移肿瘤抗原特异性T细胞杀伤体内相关抗原黑色素瘤细胞的研究分别为∼3×10~5/ml胶原纤维蛋白凝胶和∼3×10~6/ml或/g黑色素瘤。在胶原纤维蛋白凝胶中杀灭2×107/ml表达同源抗原的黑色素瘤细胞所需的抗原特异性CD8+T细胞浓度为≥107/ml。
We describe a quantitative model for assessing the cytolytic activity of antigen-specific CD8+ T cells in vitro and in vivo in which the concentration of antigen-specific CD8+ T cells determines the efficiency with which these cells kill cognate antigen–expressing melanoma cells in packed cell pellets, in three-dimensional collagen-fibrin gels in vitro, and in established melanomas in vivo. In combination with a clonogenic assay for melanoma cells, collagen-fibrin gels are 4,500–5,500-fold more sensitive than the packed cell pellet–type assays generally used to measure CD8+ T cell cytolytic activity. An equation previously used to describe neutrophil bactericidal activity in vitro and in vivo also describes antigen-specific CD8+ T cell–mediated cytolysis of cognate antigen-expressing melanoma cells in collagen-fibrin gels in vitro and in transplanted tumors in vivo. We have used this equation to calculate the critical concentration of antigen-specific CD8+ T cells, which is the concentration of these cells required to hold constant the concentration of a growing population of cognate antigen-expressing melanoma cells. It is ∼3.5 × 105/ml collagen-fibrin gel in vitro and ∼3 × 106/ml or /g melanoma for previously published studies of ex vivo–activated adoptively transferred tumor antigen–specific CD8+ T cell killing of cognate antigen–expressing melanoma cells in established tumors in vivo. The antigen-specific CD8+ T cell concentration required to kill 100% of 2 × 107/ml cognate antigen-expressing melanoma cells in collagen fibrin gels is ≥107/ml of gel.
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影响因子：
5.8
作者：
Huang, SC;Ho, CT;Lin, JK
通讯作者：
Lin, JK
影响因子：
2.2
作者：
Joseph-Pietras, Debora;Carlier, Annie;Albert, Philippe
通讯作者：
Albert, Philippe
DOI：
10.1073/pnas.122244799
发表时间：
2002-06-11
影响因子：
11.1
作者：
Li, YM;Karlin, A;Silverstein, SC
通讯作者：
Silverstein, SC
影响因子：
3.9
作者：
Hofmann, UB;Houben, R;Becker, JC
通讯作者：
Becker, JC
影响因子：
56.9
作者：
Dudley, ME;Wunderlich, JR;Rosenberg, SA
通讯作者：
Rosenberg, SA