Examination of miRNAs involved in programming human T cells

Abstract

The differentiation state of CD8+ T cells is an important determinant of their ability to eradicate tumours and infection; progressive differentiation appears to lead to a decreased effectiveness. Therefore the development of effective immunotherapies depends on a better understanding of the molecular mechanisms that underlie T cell differentiation. Several key cell surface markers are down regulated as differentiation progresses so we can define CD8+ T cells into 4 main subsets (see Fig. 1). Each subset is generated by a specific transcriptional programme. Our hypothesis is that miRNAs are important in this process of T cell differentation. If you take a cancer patient’s cells, expand in vitro, and re-infuse to the patient, the phenotype of the T cell will determine its efficacy in vivo. We have found that we can pre-condition T cells using the cytokine IL21 to have a more favourable phenotype than using the traditionally used cytokine IL2 (data not shown). We aim to explore this cytokine driven differentiation process by examining the miRNAs involved.