Gene expression of TCR-alpha/beta CD4- CD8- human T cells

The origin and function of human double negative (DN) TCR-alpha/beta T cells is unknown. They are thought to contribute to the pathogenesis of systemic lupus erythematosus because they expand and accumulate in inflamed organs. Here we provide evidence that human TCR-alpha/beta CD4- CD8- DN T cells derive exclusively from activated CD8+ T cells. Freshly isolated TCR-alpha/beta DN T cells display a distinct gene expression and cytokine production profile. DN cells isolated from peripheral blood as well as DN cells derived in vitro from CD8+ T cells, produce a defined array of pro-inflammatory mediators that includes IL-1, IL-17, IFN-gama, CXCL3, and CXCL2. These results indicate that, upon activation, CD8+ T cells have the capacity to acquire a distinct phenotype that grants them inflammatory capacity. TCR-alpha-beta+ CD25- T cells from healthy human individuals were sorted into CD4+, CD8+, and CD4-CD8- T cells. Cell lysis and RNA extraction was performed immediately. RNA from each cell subset was pooled.