Bcl-2 allows effector and memory CD8+ T cells to tolerate higher expression of Bim.
Bcl-2 allows effector and memory CD8+ T cells to tolerate higher expression of Bim.
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DOI：
10.4049/jimmunol.1100102
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发表时间：
2011-05-15
期刊：
影响因子：
--
通讯作者：
Hildeman DA
中科院分区：
文献类型：
--
作者：
Kurtulus S;Tripathi P;Moreno-Fernandez ME;Sholl A;Katz JD;Grimes HL;Hildeman DA
随着急性感染的消退，大多数效应CD8+ T细胞死亡，而一些持续存在并成为记忆T细胞。最近的研究表明，通过杀伤细胞凝集素样受体G1 （KLRG1）和CD127的相互表达鉴定的效应CD8+ T细胞亚群具有不同的寿命。与之前的报道类似，我们发现效应CD8+ T细胞具有较长的寿命（即KLRG1lowCD127high），与寿命较短的KLRG1highCD127low相比，Bcl-2水平升高。令人惊讶的是，我们发现与KLRG1highCD127low细胞相比，这些效应KLRG1lowCD127high的CD8+ T细胞的Bim水平也有所增加。在记忆细胞中也观察到类似的效果，CD8+中枢记忆T细胞比CD8+效应记忆T细胞表达更高水平的Bim和Bcl-2。使用药理学和遗传学方法，我们发现效应和记忆CD8+ T细胞亚群的存活都需要Bcl-2来对抗Bim的促凋亡活性。有趣的是，Bcl-2的抑制或缺失导致存活的效应T细胞和记忆T细胞中Bim的表达显著降低。此外，IL-7或IL-15对Bcl-2水平的操纵也影响了效应CD8+ T细胞中Bim的表达。最后，我们发现在缺乏Bax和Bak的效应CD8+ T细胞中，Bim水平显著升高。综上所述，这些数据表明，在反应收缩期间，具有最高水平Bim的细胞被选中，而Bcl-2决定了效应T细胞和记忆T细胞可以耐受的Bim水平。
As acute infections resolve, most effector CD8+ T cells die, whereas some persist and become memory T cells. Recent work showed that subsets of effector CD8+ T cells, identified by reciprocal expression of killer cell lectin-like receptor G1 (KLRG1) and CD127, have different lifespans. Similar to previous reports, we found that effector CD8+ T cells reported to have a longer lifespan (i.e., KLRG1lowCD127high) have increased levels of Bcl-2 compared with their shorter-lived KLRG1highCD127low counterparts. Surprisingly, we found that these effector KLRG1lowCD127high CD8+ T cells also had increased levels of Bim compared with KLRG1highCD127low cells. Similar effects were observed in memory cells, in which CD8+ central memory T cells expressed higher levels of Bim and Bcl-2 than did CD8+ effector memory T cells. Using both pharmacologic and genetic approaches, we found that survival of both subsets of effector and memory CD8+ T cells required Bcl-2 to combat the proapoptotic activity of Bim. Interestingly, inhibition or absence of Bcl-2 led to significantly decreased expression of Bim in surviving effector and memory T cells. In addition, manipulation of Bcl-2 levels by IL-7 or IL-15 also affected expression of Bim in effector CD8+ T cells. Finally, we found that Bim levels were significantly increased in effector CD8+ T cells lacking Bax and Bak. Together, these data indicate that cells having the highest levels of Bim are selected against during contraction of the response and that Bcl-2 determines the level of Bim that effector and memory T cells can tolerate.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.1073/pnas.2336198100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Pellegrini, M;Belz, G;Strasser, A
通讯作者：
Strasser, A
影响因子：
30.5
作者：
Kaech, SM;Tan, JT;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
4.4
作者：
Chougnet, Claire A.;Tripathi, Pulak;Hildeman, David A.
通讯作者：
Hildeman, David A.