Accumulation of cytolytic CD8+ T cells in B16-melanoma and proliferation of mature T cells in TIS21-knockout mice after T cell receptor stimulation
Accumulation of cytolytic CD8+ T cells in B16-melanoma and proliferation of mature T cells in TIS21-knockout mice after T cell receptor stimulation
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DOI：
10.1016/j.yexcr.2014.07.028
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发表时间：
2014-10-01
影响因子：
3.7
通讯作者：
Lim, In Kyoung
中科院分区：
文献类型：
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作者：
Ryu, Min Sook;Woo, Min-Yeong;Lim, In Kyoung
通过使用从TIS21敲除（KO）（2）小鼠分离的MO5黑色素瘤原位移植物和脾细胞，探索TIS21基因对成熟T细胞活化和抗肿瘤活性的体内和体外影响。与野生型（WT）（3）细胞相比，KO中成熟T细胞的增殖和存活显著增加，表明TIS 21抑制成熟T细胞增殖的速率及其存活。在MO5黑色素瘤原位移植模型中，KO小鼠在肿瘤细胞注射后沿着与WT相比肿瘤体积减小，在大约14天将更多的CD8（+）T细胞募集到肿瘤中。KO小鼠脾细胞中颗粒酶B+ CD8（+）T细胞的频率较WT小鼠增加，这可能是TIS 21基因在黑色素瘤原位移植瘤中产生抗肿瘤免疫的原因。相比之下，KO小鼠脾细胞中CD107a（+）CD8（+）T细胞频率的降低可能会影响第19天左右移植物中CD8（+）T细胞浸润的丧失。这些结果表明，TIS 21在成熟T细胞中表现出抗增殖和促凋亡作用，并且差异性地影响颗粒酶B+ CD8（+）T细胞和CD107 a（+）CD8（+）T细胞的频率，从而瞬时调节体内抗肿瘤免疫。(C)2014爱思唯尔公司All rights reserved.
In vivo and in vitro effects of TIS21 gene on the mature T cell activation and antitumor activities were explored by employing MO5 melanoma orthograft and splenocytes isolated from the TIS21-knockout (KO)(2) mice. Proliferation and survival of mature T cells were significantly increased in the KO than the wild type (WT)(3) cells, indicating that TIS21 inhibits the rate of mature T cell proliferation and its survival. In MO5 melanoma orthograft model, the KO mice recruited much more CD8(+) T cells into the tumors at around day 14 after tumor cell injection along with reduced tumor volumes compared with the WT. The increased frequency of granzyme B+ CD8(+) T cells in splenocytes of the KO mice compared with the WT may account for antitumor-immunity of TIS21 gene in the melanoma orthograft. In contrast, reduced frequencies of CD107a(+) CD8(+) T cells in the splenocytes of KO mice may affect the loss of CD8(+) T cell infiltration in the orthograft at around day 19. These results indicate that TIS21 exhibits antiproliferative and proapoptotic effects in mature T cells, and differentially affects the frequencies of granzyme B+ CD8(+) T-cells and CD107a(+) CD8(+) T-cells, thus transiently regulating in vivo anti-tumor immunity. (C) 2014 Elsevier Inc. All rights reserved.