International Immunology Advance Access originally published online on June 21, 2004
International Immunology 2004 16(8):1109-1124; doi:10.1093/intimm/dxh112
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© 2004 The Japanese Society for Immunology
ORIGINAL RESEARCH PAPERS |
Gene expression profiles during human CD4+ T cell differentiation
1 Gladstone Institute of Virology and Immunology, University of California at San Francisco, San Francisco, CA 94141, USA
2 Department of Medicine and 3 Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA
4 Genomics Core Laboratory, Gladstone Institute of Cardiovascular Disease, University of California at San Francisco, San Francisco, CA 94141, USA
5 General Clinical Research Center, Core Genomics Laboratory, San Francisco General Hospital, San Francisco, CA 94110, USA
6 Department of Obstetrics, Gynecology, and Reproductive Biology, San Francisco General Hospital, San Francisco, CA 94110, USA
Correspondence to: J. M. McCune; E-mail: mmccune{at}gladstone.ucsf.edu
To develop a comprehensive catalogue of phenotypic and functional parameters of human CD4+ T cell differentiation stages, we have performed microarray gene expression profiling on subpopulations of human thymocytes and circulating naive CD4+ T cells, including CD3–CD4+CD8– intrathymic T progenitor cells, CD3intCD4+CD8+ ‘double positive’ thymocytes, CD3highCD4+CD8– ‘single positive’ thymocytes, CD3+CD4+CD8– CD45RA+CD62L+ naive T cells from cord blood and CD3+CD4+CD8– CD45RA+CD62L+ naive T cells from adult blood. These subpopulations were sort-purified to >98% purity and their expressed RNAs were analyzed on Affymetrix Human Genome U133 arrays. Comparison of gene expression signals between these subpopulations and with early passage fetal thymic stromal cultures identify: (i) transcripts that are preferentially expressed in human CD4+ T cell subpopulations and not in thymic stromal cells; (ii) major shifts in gene expression as progenitor T cells mature into progeny; (iii) preferential expression of transcripts at the progenitor cell stage with plausible relevance to the regulation of expansion and differentiation of these cells; and (iv) preferential expression of potential markers of recent thymic emigrants in naive-phenotype CD4+ T cells from cord blood. Further evaluation of these findings may lead to a better definition of human thymopoiesis as well as to improved approaches to monitor and to augment the function of this important organ of T cell production.
Keywords: gene expression, microarray, naive CD4+ T cell, recent thymic emigrants, thymocytes
Transmitting editor: P. W. Kincade
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