Sensitive Gene Expression Profiling of Human T Cell Subsets Reveals Parallel Post-Thymic Differentiation for CD4+ and CD8+ Lineages

• Published in: The Journal of immunology (1950) 2007-12, Vol.179 (11), p.7406-7414
• Main Authors: Appay, Victor, Bosio, Andreas, Lokan, Stefanie, Wiencek, Yvonne, Biervert, Christian, Kusters, Daniel, Devevre, Estelle, Speiser, Daniel, Romero, Pedro, Rufer, Nathalie, Leyvraz, Serge
• Format: Article
• Language: English
• Subjects: CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Cell Differentiation - immunology; Cell Line; Cell Lineage - immunology; DNA, Complementary - genetics; Gene Expression Profiling; Human health and pathology; Humans; Life Sciences; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; T-Lymphocyte Subsets - immunology; Thymus Gland - cytology; Thymus Gland - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.179.11.7406

The differentiation of CD4(+) or CD8(+) T cells following priming of naive cells is central in the establishment of the immune response against pathogens or tumors. However, our understanding of this complex process and the significance of the multiple subsets of differentiation remains controversial. Gene expression profiling has opened new directions of investigation in immunobiology. Nonetheless, the need for substantial amount of biological material often limits its application range. In this study, we have developed procedures to perform microarray analysis on amplified cDNA from low numbers of cells, including primary T lymphocytes, and applied this technology to the study of CD4 and CD8 lineage differentiation. Gene expression profiling was performed on samples of 1000 cells from 10 different subpopulations, defining the major stages of post-thymic CD4(+) or CD8(+) T cell differentiation. Surprisingly, our data revealed that while CD4(+) and CD8(+) T cell gene expression programs diverge at early stages of differentiation, they become increasingly similar as cells reach a late differentiation stage. This suggests that functional heterogeneity between Ag experienced CD4(+) and CD8(+) T cells is more likely to be located early during post-thymic differentiation, and that late stages of differentiation may represent a common end in the development of T-lymphocytes.