International Immunology, Vol. 15, No. 10, pp. 1237-1248,
October 2003
© 2003 Japanese Society for Immunology
Gene expression analysis of thymocyte selection in vivo
1 Laboratory of Immunobiology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
Correspondence to: E. L. Reinherz; E-mail: ellis_reinherz{at}dfci.harvard.edu
Transmitting editor: S. Koyasu
Self versus non-self discrimination is a key feature of immunorecognition. Through TCR-activated apoptotic mechanisms, autoreactive thymocytes are purged at the CD4+CD8+ double-positive (DP) precursor stage prior to maturation to CD4+ or CD8+ single-positive (SP) thymocytes. To investigate this selection process in vivo, gene expression analysis by oligonucleotide array was performed in TCR transgenic mice. In total, 244 differentially expressed DP thymocyte genes induced or repressed by TCR triggering in vivo were identified. Genes involved in the biological processes of apoptosis, DNA recombination, antigen processing and adhesion are coordinately engaged. Moreover, analysis of gene expression in thymocyte subsets revealed that TCR ligand-induced expression profiles vary according to their developmental stage, with 48 genes showing DP preference and nine showing SP thymocyte preference. Finally, our data suggest that both the extrinsic and the intrinsic apoptosis pathways are operating in thymic selection.
Keywords: apoptosis, DNA microarray, gene profiling, T cell differentiation, thymus
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