IL-2 regulates perforin and granzyme gene expression in CD8+ T cells independently of its effects on survival and proliferation

被引:105
作者
Janas, ML
Groves, P
Kienzle, N
Kelso, A [1 ]
机构
[1] Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia
[2] Cooperat Res Ctr Vaccine Technol, Brisbane, Qld, Australia
关键词
D O I
10.4049/jimmunol.175.12.8003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Perforin and the serine protease granzymes are key effectors of CD8(+) T cell granule-mediated cytotoxicity, but the requirements for their expression remain largely undefined. We show in this study that IL-2 increased the expression of perforin and granzyme A, B, and C mRNA; intracellular granzyme B protein levels; and cytolytic function in a dose-dependent manner during primary activation of murine CD8(+) T cells in vitro. Two approaches showed that these responses were not a consequence of the effects of IL-2 on cell survival and proliferation. First, IL-2 enhancement of perforin and granzyme expression was equivalent in CD8(+) T cells from wild-type and bcl-2 transgenic mice, although only the latter cells survived in low concentrations or the absence of added IL-2. This property of bcl-2 transgenic T cells also allowed the demonstration that induction of granzyme A, B, and C mRNA and granzyme B protein required exogenous IL-2, whereas induction of perforin and IFN-gamma expression did not. Second, analysis of perforin and granzyme mRNA levels in cells separated according to division number using the dye CFSE showed that the effects of IL-2 were unrelated to division number. Together, these findings indicate that IL-2 can directly regulate perforin and granzyme gene expression in CD8(+) T cells independently of its effects on cell survival and proliferation.
引用
收藏
页码:8003 / 8010
页数:8
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