Inhibition of tumor growth by NK1.1+ cells and CD8+ T cells activated by IL-15 through receptor beta/common gamma signaling in trans.
Inhibition of tumor growth by NK1.1+ cells and CD8+ T cells activated by IL-15 through receptor beta/common gamma signaling in trans.
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DOI：
10.4049/jimmunol.181.12.8237
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发表时间：
2008-12-15
期刊：
影响因子：
--
通讯作者：
Wu TC
中科院分区：
文献类型：
--
作者：
Rowley J;Monie A;Hung CF;Wu TC
IL-15是参与CD 8 + T细胞和NK细胞的存活和功能的重要细胞因子。IL-15可由IL-15 R α（IL-15 RA）呈递，以与共享的IL-2/IL-15 R β和共同的γ链结合，从而激活NK细胞和CD 8 + T细胞上的信号传导途径。在本研究中，我们使用用编码IL-15连接到IL-15 RA的逆转录病毒转导的TC-1肿瘤细胞（IL-15/IL-15 RA）来表征反式呈递的IL-15对NK细胞和CD 8 + T细胞的功能。我们证明了TC-1细胞上IL-15/IL-15 RA的表达导致肿瘤浸润NK细胞、NKT细胞和CD 8 + T细胞的百分比增加，从而抑制了攻击小鼠中的肿瘤生长。此外，体内Ab耗竭实验表明，NK 1.1+细胞和CD 8 + T细胞在这种肿瘤生长抑制中是重要的。此外，通过IL-15上的共同γ链结合位点中的单个氨基酸突变消除了这种免疫细胞的积累和肿瘤生长的抑制。我们还观察到IL-15/IL-15 RA转导的TC-1细胞导致NK和CD 8 + T细胞中STAT 5的反式激活，这在突变的IL-15/IL-15 RA转导的TC-1细胞中被消除。综上所述，我们的数据表明，共有的IL-15/IL-2 R β/共同γ信号通路的共同γ链结合依赖性激活可能在NK细胞和CD 8 + T细胞的激活中发挥重要作用，导致IL-15/IL-15 RA反式呈递介导的肿瘤生长抑制。
IL-15 is an important cytokine involved in the survival and function of CD8+ T cells and NK cells. IL-15 can be presented by IL-15Rα (IL-15RA) to bind with the shared IL-2/IL-15Rβ and common γ-chains, which activate signaling pathways on NK cells and CD8+ T cells. In the present study, we characterized the function of trans-presented IL-15 on NK cells and CD8+ T cells using TC-1 tumor cells transduced with a retrovirus encoding IL-15 linked to IL-15RA (IL-15/IL-15RA). We demonstrated that the expression of IL-15/IL-15RA on TC-1 cells led to increased percentages of tumor-infiltrating NK cells, NKT cells, and CD8+ T cells, resulting in the inhibition of tumor growth in challenged mice. Additionally, in vivo Ab depletion experiments demonstrated that NK1.1+ cells and CD8+ T cells were important in this inhibition of tumor growth. Furthermore, this accumulation of immune cells and inhibition of tumor growth was abolished by a single amino acid mutation in the common γ-chain binding site on IL-15. We also observed that IL-15/IL-15RA-transduced TC-1 cells led to the activation of STAT5 in NK and CD8+ T cells in trans, which was abolished in the mutated IL-15/IL-15RA-transduced TC-1 cells. Taken together, our data suggest that common γ-chain binding-dependent activation of the shared IL-15/IL-2Rβ/common γ signaling pathway may play an important role in the activation of NK cells and CD8+ T cells, resulting in IL-15/IL-15RA trans-presentation-mediated inhibition of tumor growth.
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影响因子：
15.3
作者：
Goldrath, Ananda W;Sivakumar, Pallavur V;Glaccum, Moira;Kennedy, Mary K;Bevan, Michael J;Benoist, Christophe;Mathis, Diane;Butz, Eric A
通讯作者：
Butz, Eric A
影响因子：
11.4
作者：
GIRI, JG;KUMAKI, S;ANDERSON, DM
通讯作者：
ANDERSON, DM
影响因子：
4.4
作者：
Kelly, J;Spolski, R;Leonard, WJ
通讯作者：
Leonard, WJ
影响因子：
5.1
作者：
Hung, C-F;Tsai, Y-C;Wu, T-C
通讯作者：
Wu, T-C
影响因子：
20.3
作者：
Kobayashi, H;Dubois, S;Tagaya, Y
通讯作者：
Tagaya, Y