Gene expression profiles during human CD4+ T cell differentiation

Abstract

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. © 2004 The Japanese Society for Immunology.