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* Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom;
Medical Research Council Rosalind Franklin Centre for Genomics Research, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom;
University School of Medicine, Shigenobu, Ehime, Japan; and
Division of Medicine, Imperial College London, and Department of Rheumatology, Chelsea and Westminster Hospital, London, United Kingdom
Memory T cells are heterogeneous in terms of their phenotype and functional properties. We investigated the molecular profiles of human CD8 naive central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells using gene expression microarrays and phospho-protein-specific intracellular flow cytometry. We demonstrate that TCM have a gene expression and cytokine signaling signature that lies between that of naive and TEM or TEMRA cells, whereas TEM and TEMRA are closely related. Our data define the molecular basis for the different functional properties of central and effector memory subsets. We show that TEM and TEMRA cells strongly express genes with known importance in CD8 T cell effector function. In contrast, TCM are characterized by high basal and cytokine-induced STAT5 phosphorylation, reflecting their capacity for self-renewal. Altogether, our results distinguish TCM and TEM/TEMRA at the molecular level and are consistent with the concept that TCM represent memory stem cells.
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