Identification of T cell-restricted genes, and signatures for different T cell responses, using a comprehensive collection of microarray datasets.
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 alphabeta+ and gammadelta+, 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 gammadelta T cells expressed no unique gene transcripts, but did differ from alphabeta 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.
Chtanova
Tatyana
T
Garvan Institute of Medical Research, Darlinghurst, Australia.
Newton
Rebecca
R
Liu
Sue M
SM
Weininger
Lilach
L
Young
Timothy R
TR
Silva
Diego G
DG
Bertoni
Francesco
F
Rinaldi
Andrea
A
Chappaz
Stephane
S
Sallusto
Federica
F
Rolph
Michael S
MS
Mackay
Charles R
CR
D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology
D012333:RNA, Messenger