Evidence of a novel IL-2/15Rβ-targeted cytokine involved in homeostatic proliferation of memory CD8+ T cells
Evidence of a novel IL-2/15Rβ-targeted cytokine involved in homeostatic proliferation of memory CD8+ T cells
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DOI：
10.4049/jimmunol.173.10.6041
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发表时间：
2004-11-15
影响因子：
4.4
通讯作者：
Hirano, T
中科院分区：
文献类型：
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作者：
Kamimura, D;Ueda, N;Hirano, T
记忆性CD8(+) T细胞的稳态受细胞因子的调控。IL-15可促进记忆性CD8(+) T细胞的增殖，而IL-2可抑制其在体内的分裂。IL-2的这种抑制作用似乎是通过其他细胞群间接发生的，包括CD25(+)CD4(+) T细胞；然而，这一机制的细节尚不清楚。在这项研究中，我们发现1)ag经历型和记忆型CD8(+) T细胞在体内IL-2耗尽后分裂；2)在IL-15敲除（KO）和il -7缺失的IL-15 KO小鼠中，IL-2缺失后产生CD44（高）IL-2/ 15rbeta（高）CD8(+) T细胞。3)令人惊讶的是，在IL-2缺失的IL-15 KO小鼠中，IL-2/ 15rbeta信号的阻断完全消除了记忆性CD8(+) T细胞的分裂，尽管已知唯一通过IL-2/ 15rbeta起作用的细胞因子是IL-2和IL-15；4) IL-2缺失诱导记忆性CD8(+) T细胞分裂需要IL-2/ 15rbeta分子的表达。这些结果表明，体内IL-2的消耗通过il -15独立但IL-2/ 15rbeta依赖的机制诱导记忆性CD8(+) T细胞分裂，这表明存在一种新的利用IL-2/ 15rbeta的细胞因子直接作用于记忆性CD8(+) T细胞以促进细胞分裂。
The homeostasis of memory CD8(+) T cells is regulated by cytokines. IL-15 is shown to promote the proliferation of memory CD8(+) T cells, while IL-2 suppresses their division in vivo. This inhibitory effect of IL-2 appears to occur indirectly, through other cell populations including CD25(+)CD4(+) T cells; however, the details of this mechanism remain unclear. In this study, we show that 1) both Ag-experienced and memory phenotype CD8(+) T cells divided after the depletion of IL-2 in vivo; 2) this division occurred normally and CD44(high)IL-2/15Rbeta(high) CD8(+) T cells generated after IL-2 depletion in IL-15 knockout (KO) and in IL-7-depleted IL-15 KO mice; 3) surprisingly, the blockade of IL-2/15Rbeta signaling in IL-2-depleted IL-15 KO mice completely abolished the division of memory CD8(+) T cells, although the only cytokines known to act through IL-2/15Rbeta are IL-2 and IL-15; and 4) the expression of IL-2/15Rbeta molecules on memory CD8(+) T cells was required for their division induced by IL-2 depletion. These results demonstrate that the depletion of IL-2 in vivo induced memory CD8(+) T cell division by an IL-15-independent but by an IL-2/15Rbeta-dependent mechanism, suggesting the existence of a novel IL-2/15Rbeta-utilizing cytokine that acts directly on memory CD8(+) T cells to promote cell division.