Transcript imaging of the development of human T helper cells using oligonucleotide arrays

Many pathological processes, including those causing allergies and autoimmu ne diseases, are associated with the presence of specialized subsets of T h elper cells at the site of inflammation(1) Understanding the genetic progra m that controls the functional properties of T helper type 1 (Th1) versus T helper type 2 (Th2) cells may provide insight into the pathophysiology of inflammatory diseases. We compared the gene-expression profiles of human Th 1 and Th2 cells using high-density oligonucleotide arrays with the capacity to display transcript levels of 6,000 human genes'. Here we analyse the da ta sets derived from five independent experiments using statistical algorit hms. This approach resulted in the identification of 215 differentially exp ressed genes, encoding proteins involved in transcriptional regulation, apo ptosis, proteolysis, and cell adhesion and migration. A-subset of these gen es was further upregulated by exposure of differentiated Th1 cells to inter leukin-12 (IL-12), as confirmed by kinetic PCR analysis, indicating that IL -12 modulates the effector functions of Th1 cells in the absence of antigen ic stimulation. Functional assays and in vivo expression of selected genes have validated the biological relevance of our study. Our results provide n ew insight into the transcriptional program controlling the functional dive rsity of subsets of T helper cells.