Gene Microarrays Reveal Extensive Differential Gene Expression in Both CD4+ and CD8+ Type 1 and Type 2 T Cells

An important subdivision of effector T cells can be made based on patterns of cytokine production and functional programs. Type 1 T cells produce IFN-gamma and protect against viral pathogens, whereas type 2 cells produce cytokines such as IL-4 and IL-5 and protect against large extracellular parasites. Both CD4(+) and CD8(+) T cells can be polarized into type 1 or type 2 cytokine-secreting cells, suggesting that both populations play a regulatory role in immune responses. In this study, we used high-density oligonucleotide arrays to produce a comprehensive picture of gene expression in murine CD4(+) Th1 and Th2 cells, as well as CD8(+) type 1 and type 2 T cells. Polarized type 1 and 2 cells transcribed mRNA for an unexpectedly large number of genes, most of which were expressed in a similar fashion between type 1 and type 2 cells. However, >100 differentially expressed genes were identified for both the CD4(+) and CD8(+) type 1 and 2 subsets, many of which have not been associated with T cell polarization. These genes included cytokines, transcription factors, molecules involved in cell migration, as well as genes with unknown function. The program for type 1 or type 2 polarization was similar for CD4(+) and CD8(+) cells, since gene expression patterns were roughly the same. The expression of select genes was confirmed using real-time PCR. The identification of genes associated with T cell polarization may give important insights into functional and phenotypic differences between effector T cell subsets and their role in normal responses and inflammatory disease.