Differential expression of granzyme B and C in murine cytotoxic lymphocytes.
Differential expression of granzyme B and C in murine cytotoxic lymphocytes.
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DOI：
10.4049/jimmunol.0804333
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发表时间：
2009-05-15
期刊：
影响因子：
--
通讯作者：
Ley TJ
中科院分区：
文献类型：
--
作者：
Cai SF;Fehniger TA;Cao X;Mayer JC;Brune JD;French AR;Ley TJ
细胞毒性淋巴细胞利用颗粒胞吐途径杀死病原体感染细胞和肿瘤细胞。尽管这一途径中的许多基因已被广泛表征（如穿孔素、颗粒酶A和B），但颗粒酶C的作用尚不清楚。因此，我们开发了一种颗粒酶C特异性单抗，并使用流式细胞术检测了颗粒酶B基因缺失的野生型和突变型GzmB - / - cre小鼠淋巴细胞室中颗粒酶B和C的表达。我们检测了CD3/CD28微球或MLRs激活的CD4+和CD8+ T细胞中颗粒酶B和C的表达。体外用IL-15刺激NK细胞也能诱导这两种颗粒酶的表达。在野生型淋巴细胞中，相对于颗粒酶B，颗粒酶C的上调被延迟，而GzmB - / - cre细胞更早且更丰富地表达颗粒酶C，这表明颗粒酶B基因中缺失的350-bp区域对颗粒酶B和颗粒酶C的调控都很重要。定量RT-PCR显示，颗粒酶C蛋白水平受mRNA丰度的调控。在体内，野生型CD8αα+上皮内淋巴细胞组成性地表达颗粒酶B， GzmB - / - cre上皮内淋巴细胞同样表达颗粒酶C。通过小鼠CMV持续感染模型，我们检测到了受感染宿主NK细胞中颗粒酶C的延迟表达。综上所述，这些发现表明，颗粒酶C在持续的抗原刺激下被激活，当颗粒酶B失效时，为宿主提供非冗余的备份保护。
Cytotoxic lymphocytes use the granule exocytosis pathway to kill pathogen-infected cells and tumor cells. Although many genes in this pathway have been extensively characterized (e.g., perforin, granzymes A and B), the role of granzyme C is less clear. We therefore developed a granzyme C-specific mAb and used flow cytometry to examine the expression of granzyme B and C in the lymphocyte compartments of wild-type and mutant GzmB−/− cre mice, which have a small deletion in the granzyme B gene. We detected granzyme B and C expression in CD4+ and CD8+ T cells activated with CD3/CD28 beads or MLRs. Stimulation of NK cells in vitro with IL-15 also induced expression of both granzymes. Granzyme C up-regulation was delayed relative to granzyme B in wild-type lymphocytes, whereas GzmB−/− cre cells expressed granzyme C earlier and more abundantly on a per-cell basis, suggesting that the deleted 350-bp region in the granzyme B gene is important for the regulation of both granzymes B and C. Quantitative RT-PCR revealed that granzyme C protein levels were regulated by mRNA abundance. In vivo, a population of wild-type CD8αα+ intraepithelial lymphocytes constitutively expressed granzyme B and GzmB−/− cre intraepithelial lymphocytes likewise expressed granzyme C. Using a model of a persistent murine CMV infection, we detected delayed expression of granzyme C in NK cells from infected hosts. Taken together, these findings suggest that granzyme C is activated with persistent antigenic stimulation, providing nonredundant backup protection for the host when granzyme B fails.
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颗粒酶B介导的细胞色素C释放受BCL-2家族成员的竞标和BAX的调节。
影响因子：
15.3
作者：
Heibein, J A;Goping, I S;Barry, M;Pinkoski, M J;Shore, G C;Green, D R;Bleackley, R C
通讯作者：
Bleackley, R C
影响因子：
56.9
作者：
Brown, MG;Dokun, AO;Yokoyama, WM
通讯作者：
Yokoyama, WM
影响因子：
32.4
作者：
Cao, Xuefang;Cai, Sheng F.;Ley, Timothy J.
通讯作者：
Ley, Timothy J.
影响因子：
4.4
作者：
Kelso, A;Costelloe, EO;Fitzpatrick, DR
通讯作者：
Fitzpatrick, DR
DOI：
10.4049/jimmunol.181.11.7810
发表时间：
2008-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Getachew Y;Stout-Delgado H;Miller BC;Thiele DL
通讯作者：
Thiele DL