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

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. Overall design: 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.

人类双阴性（DN，double negative）T细胞受体αβ（TCR-α/β）T细胞的起源与功能迄今尚未明确。该类细胞被认为与系统性红斑狼疮（systemic lupus erythematosus）的发病机制相关，因其可在炎症器官中扩增并聚集。本研究提供证据表明，人类TCR-α/β型CD4⁻CD8⁻双阴性T细胞仅起源于活化的CD8⁺T细胞。新鲜分离的TCR-α/β型双阴性T细胞呈现独特的基因表达谱与细胞因子分泌特征。从外周血分离的双阴性T细胞，以及体外由CD8⁺T细胞诱导生成的双阴性T细胞，均可分泌一系列明确的促炎介质，包括IL-1、IL-17、γ干扰素（IFN-γ）、CXCL3与CXCL2。上述结果表明，CD8⁺T细胞在活化后可获得独特的细胞表型，从而具备促炎能力。实验总体设计：从健康人体中分离得到TCR-α/β⁺CD25⁻T细胞，将其分选为CD4⁺、CD8⁺及CD4⁻CD8⁻T细胞亚群。随后立即进行细胞裂解与RNA提取，并将各细胞亚群的RNA进行混合。