Proteomics Analysis of Naturally Occurring CD4+/CD25+ Regulatory T Cells.
Journal - ASH Annual Meeting Abstracts
Recently, a naturally occurring regulatory T cell population(Tregs) has been identified and shown to actively suppress immuneresponses of self-reactive T cells. The molecular basis forthe function of Tregs remains unclear. We are interested inidentifying molecules specifically expressed in human Tregsthat are candidates for mediating suppression by comparativeproteomic and transcriptomic analysis of human CD4+/CD25+ andCD4+/CD25- T cells using two-dimensional electrophoresis (2-DE)followed by electrospray tandem MS on the Micromass Q-Tof (HPLC-MS/MS)and high-density cDNA microarray technology, respectively. Thusfar, the most revealing results of the 2-DE analysis are thedetection of an upregulation in the expression of a proteinkinase inhibitor and FUSE binding protein (FBP), a regulatorof c-Myc expression. The gene expression pattern of the Tregswas overall very similar compared to CD4+/CD25- T cells despitetheir major functional differences. We have identified severalsets of genes differentially expressed in the Tregs. Of specialinterest are adhesion molecules and chemokine receptors thatcould reveal distinct trafficking patterns. We are in the processof validating and screening at the protein level several ofthese candidate genes that could lead to the identificationof specific molecular events in the Tregs. The upregulationof the PKC inhibitor is especially interesting, as the reductionof IL-2 production may explain the hypoproliferative statusof Tregs. The increase in FBP and a resulting increase in c-Myctranscription may promote the survival of Tregs, thereby contributingto the prevention of autoimmunity.FootnotesDisclosure: No relevant conflicts of interest to declare.