Gene expression profiles during human CD4+ T cell differentiation.
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, CD3(int)CD4(+)CD8(+) 'double positive' thymocytes, CD3(high)CD4(+)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.
Lee
Myeong Sup
MS
Gladstone Institute of Virology and Immunology, University of California at San Francisco, San Francisco, CA 94141, USA.
Hanspers
Kristina
K
Barker
Christopher S
CS
Korn
Abner P
AP
McCune
Joseph M
JM
D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D015703:Antigens, CD