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The Journal of Immunology, 2005, 175: 7837-7847.
Copyright © 2005 by The American Association of Immunologists

Identification of T Cell-Restricted Genes, and Signatures for Different T Cell Responses, Using a Comprehensive Collection of Microarray Datasets1

Tatyana Chtanova*,¶, Rebecca Newton*, Sue M. Liu*,¶, Lilach Weininger*, Timothy R. Young*, Diego G. Silva{dagger}, Francesco Bertoni{ddagger}, Andrea Rinaldi§, Stephane Chappaz§, Federica Sallusto§, Michael S. Rolph*,¶ and Charles R. Mackay2,*,¶

* Garvan Institute of Medical Research, Darlinghurst, Australia; {dagger} Australian National University Medical School, Canberra, Australia; {ddagger} Experimental Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; § Institute for Research in Biomedicine, Bellinzona, Switzerland; and Cooperative Research Center for Asthma, University of Sydney, Camperdown, Australia

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.




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