Identification of T cell-restricted genes, and signatures for different T cell responses, using a comprehensive collection of microarray datasets
Identification of T cell-restricted genes, and signatures for different T cell responses, using a comprehensive collection of microarray datasets
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DOI：
10.4049/jimmunol.175.12.7837
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发表时间：
2005-12-15
影响因子：
4.4
通讯作者：
Mackay, CR
中科院分区：
文献类型：
--
作者：
Chtanova, T;Newton, R;Mackay, CR
我们使用了Affymetrix微阵列数据集的全面收集来确定哪些基因或分子区分了人类T细胞的已知主要亚群。我们的策略使我们能够识别在大多数T细胞亚群中表达的基因：TCRαβ(+)和Gamma Delta(+)，三个效应亚群(Th1，Th2和T滤泡辅助细胞)，T中央记忆，T效应记忆，激活的T细胞，以及其他。我们的基因芯片数据集还允许识别由T细胞优先或排他性表达的基因，而不是所描述的大量非T细胞白细胞亚群。微阵列数据集之间的交叉比较揭示了某些子集的重要特征。例如，血液中的伽马-德尔塔T细胞没有表达独特的基因转录本，但在许多下调的基因上确实与阿尔法-贝塔T细胞不同。对T细胞亚群之间差异表达的所有基因进行等级聚类，能够识别准确的签名。此外，不同的T细胞亚群可以通过较小的预测基因子集在基因表达水平上进行区分，其中大多数以前没有与任何单独的亚集直接相关。T细胞激活对基因调控的影响最大，而中央记忆T细胞和效应记忆T细胞表现出惊人的相似基因表达谱。对T细胞基本活动的基因表达模式的了解，如激活、各种效应功能和免疫记忆，为更好地理解T细胞及其在免疫防御中的作用提供了基础。
We used a comprehensive collection of Affymetrix microarray datasets to ascertain which genes or molecules distinguish the known major subsets of human T cells. Our strategy allowed us to identify the genes expressed in most T cell subsets: TCR alpha beta(+) and gamma delta(+), three effector subsets (Th1, Th2, and T follicular helper cells), T central memory, T effector memory, activated T cells, and others. Our genechip dataset also allowed for identification of genes preferentially or exclusively expressed by T cells, compared with numerous non-T cell leukocyte subsets profiled. Cross-comparisons between microarray datasets revealed important features of certain subsets. For instance, blood gamma delta T cells expressed no unique gene transcripts, but did differ from alpha beta T cells in numerous genes that were down-regulated. Hierarchical clustering of all the genes differentially expressed between T cell subsets enabled the identification of precise signatures. Moreover, the different T cell subsets could be distinguished at the level of gene expression by a smaller subset of predictor genes, most of which have not previously been associated directly with any of the individual subsets. T cell activation had the greatest influence on gene regulation, whereas central and effector memory T cells displayed surprisingly similar gene expression profiles. Knowledge of the patterns of gene expression that underlie fundamental T cell activities, such as activation, various effector functions, and immunological memory, provide the basis for a better understanding of T cells and their role in immune defense.