Identification of an evolutionarily conserved transcriptional signature of CD8 memory differentiation that is shared by T and B cells.
Identification of an evolutionarily conserved transcriptional signature of CD8 memory differentiation that is shared by T and B cells.
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DOI：
10.4049/jimmunol.181.3.1859
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发表时间：
2008-08-01
期刊：
影响因子：
--
通讯作者：
Golub TR
中科院分区：
文献类型：
--
作者：
Haining WN;Ebert BL;Subrmanian A;Wherry EJ;Eichbaum Q;Evans JW;Mak R;Rivoli S;Pretz J;Angelosanto J;Smutko JS;Walker BD;Kaech SM;Ahmed R;Nadler LM;Golub TR
抗原接触后，幼稚淋巴细胞分化成记忆细胞群，这些记忆细胞群具有一组共同的功能，包括对抗原再暴露的更快反应和自我更新的能力。然而，不同淋巴细胞谱系中的记忆淋巴细胞在功能和表型上是多样的。目前尚不清楚离散的T细胞和B细胞群体在分化为记忆状态期间是否使用类似的转录程序。我们使用跨物种基因组分析，以检查在幼稚淋巴细胞分化为记忆细胞在多个人群的人CD 4，CD 8和B细胞淋巴细胞以及两个小鼠模型的记忆发展的基因上调的模式。我们确定并验证了在人类和小鼠CD8记忆分化中与幼稚细胞相比在记忆细胞中上调的基因的签名，这表明该转录程序具有明显的进化保守性。令人惊讶的是，这种保守的CD 8分化特征在CD 4和B细胞谱系的记忆分化期间也上调。为了验证这种特征的生物学意义，我们发现这种基因特征的改变可以区分慢性病毒感染小鼠模型中功能性和耗竭的CD8 T细胞。最后，我们从四聚体分选的人类T细胞中生成了全基因组微阵列数据，并显示了HIV特异性T细胞与流感特异性T细胞之间的这种分化特征的深刻差异。因此，我们的数据表明，除了谱系特异性分化程序，T和B淋巴细胞采用一个共同的转录程序在记忆的发展过程中被破坏的慢性病毒感染。
After antigen encounter, naive lymphocytes differentiate into populations of memory cells that share a common set of functions including faster response to antigen re-exposure and the ability to self-renew. However memory lymphocytes in different lymphocyte lineages are functionally and phenotypically diverse. It is not known whether discrete populations of T and B cells use similar transcriptional programs during differentiation into the memory state. We used cross-species genomic analysis to examine the pattern of genes upregulated during the differentiation of naive lymphocytes into memory cells in multiple populations of human CD4, CD8 and B cell lymphocytes as well as two mouse models of memory development. We identified and validated a signature of genes that was upregulated in memory cells compared to naive cells in both human and mouse CD8 memory differentiation, suggesting marked evolutionary conservation of this transcriptional program. Surprisingly, this conserved CD8 differentiation signature was also upregulated during memory differentiation in CD4 and B cell lineages. To validate the biologic significance of this signature we showed that alterations in this signature of genes could distinguish between functional and exhausted CD8 T cells from a mouse model of chronic viral infection. Finally, we generated genome-wide microarray data from tetramer-sorted human T cells and showed profound differences in this differentiation signature between T cells specific for HIV from those specific for influenza. Thus, our data suggest that in addition to lineage-specific differentiation programs, T and B lymphocytes employ a common transcriptional program during memory development that is disrupted in chronic viral infection.
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影响因子：
64.5
作者：
Kaech, SM;Hemby, S;Ahmed, R
通讯作者：
Ahmed, R
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