regulation and gene expression profiling of nkg2d positive human cytomegalovirus-primed cd4+ t-cellsnkg2d积极的调控和基因表达分析人类cytomegalovirus-primed cd4 + t细胞.pdfVIP

Regulation and Gene Expression Profiling of NKG2D Positive Human Cytomegalovirus-Primed CD4+ T-Cells 1 2 1 Helle Jensen *, Lasse Folkersen , Søren Skov * 1 Section of Biomedicine, Laboratory of Immunology, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark,, 2 Atherosclerosis Research Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden Abstract NKG2D is a stimulatory receptor expressed by natural killer (NK) cells, CD8+ T-cells, and cd T-cells. NKG2D expression is normally absent from CD4+ T-cells, however recently a subset of NKG2D+ CD4+ T-cells has been found, which is specific for human cytomegalovirus (HCMV). This particular subset of HCMV-specific NKG2D+ CD4+ T-cells possesses effector-like functions, thus resembling the subsets of NKG2D+ CD4+ T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4+ T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA) to investigate the gene expression profile of NKG2D+ CD4+ T-cells, generated from HCMV-primed CD4+ T-cells. We show that the HCMV-primed NKG2D+ CD4+ T-cells possess a higher differentiated phenotype than the NKG2D– CD4+ T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4+ T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4+ T-cells following HCMV stimulation. However, knock-down of C