Many pathological processes, including those causing allergies and autoimmune diseases, are associated with the presence of specialized subsets of T helper cells at the site of inflammation. Understanding the genetic program 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 Th1 and Th2 cells using high-density oligonucleotide arrays with the capacity to display transcript levels of 6,000 human genes. Here we analyse the data sets derived from five independent experiments using statistical algorithms. This approach resulted in the identification of 215 differentially expressed genes, encoding proteins involved in transcriptional regulation, apoptosis, proteolysis, and cell adhesion and migration. A subset of these genes was further upregulated by exposure of differentiated Th1 cells to interleukin-12 (IL-12), as confirmed by kinetic PCR analysis, indicating that IL-12 modulates the effector functions of Th1 cells in the absence of antigenic stimulation. Functional assays and in vivo expression of selected genes have validated the biological relevance of our study. Our results provide new insight into the transcriptional program controlling the functional diversity of subsets of T helper cells.

Gene expression profiles of five consecutive stages of mouse B cell development were generated with high-density oligonucleotide arrays from as few as 2 × 104 ex vivo isolated and flow-cytometrically purified cells. Between 2.8% and 6.8% of all genes change on differentiation from one cellular stage to the next by at least twofold. The entire pathway involves differential expression of 10.7% of all genes. Previously known expression patterns of 15 genes (like surrogate light chain, RAG-1/2, MHC class II, mel-14 antigen) are confirmed. The gene expression patterns of the proliferating pre-BI and large pre-BII cells on the one hand, and the resting immature and mature B cells on the other hand, are most similar to each other. Small pre-BII cells display a pattern that is transitional between these two groups. Most of the genes expressed in early precursors are involved in general processes, like protein folding or cell cycle regulation, whereas more mature precursors express genes involved in more specific molecular programs (cell surface receptors, secreted factors, and adhesion molecules, among others). Between 19 and 139 genes share a given expression pattern. Combining knowledge about gene function and expression pattern allows identification of novel candidate genes potentially involved in self-maintenance of pre-BI cells, allelic exclusion and pre-B cell receptor signaling in large pre BII cells, cell-cycle arrest of small pre-BII cells, propensity toward apoptosis or anergization in immature B cells, propensity toward cell division and activation in mature B cells, and stage-specific interactions with stromal cells in the bone marrow

Pax-6 genes encode evolutionarily conserved transcription factors capable of activating the gene-expression program required to build an eye. When ectopically expressed in Drosophila imaginal discs, Pax-6 genes induce the eye formation on the corresponding appendages of the adult fly. We used two different Drosophila full-genome DNA microarrays to compare gene expression in wild-type leg discs versus leg discs where eyeless, one of the two Drosophila Pax-6 genes, was ectopically expressed. We validated these data by analyzing the endogenous expression of selected genes in eye discs and identified 371 genes that are expressed in the eye imaginal discs and up-regulated when an eye morphogenetic field is ectopically induced in the leg discs. These genes mainly encode transcription factors involved in photoreceptor specification, signal transducers, cell adhesion molecules, and proteins involved in cell division. As expected, genes already known to act downstream of eyeless during eye development were identified, together with a group of genes that were not yet associated with eye formation.