Project description: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.
Project description:The aim of this study was to quantify the impact of NOD genetic vatiation on the transcriptional programs induced by the alpha beta-TCR at the DN to DP transition in the BDC2.5 TCR Tg model CD4 and CD8-complement mediated depletion followed by FACS Experiment type: BDC2.5 TCR Tg or polyclonal B6g7 versus NOD
Project description:Local administration of IFN-α-producing proliferating myeloid cells (IFN-α-iPSC-pMCs) inhibited the tumor growth not only at the treatment site but also at the distant site (left). T cell receptor (TCR)-β chain repertoire and complementarity determining region 3 (CDR3) gene sequence analyses of tumor-infiltrating lymphocytes (TILs) showed marked enrichment of T cells with identical TCR-β chains in bilateral tumor tissues.
Project description: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.
Project description:The aim of this study was to quantify the impact of NOD genetic vatiation on the transcriptional programs induced by the alpha beta-TCR at the DN to DP transition in the BDC2.5 TCR Tg model
Project description:The Ag receptors on alpha/beta and gamma/delta T cells differ not only in the nature of the ligands that they recognize but also in their signaling potential. We hypothesized that the differences in alpha/beta - and gamma/delta TCR signal transduction were due to differences in the intracellular signaling pathways coupled to these two TCRs. To investigate this, we employed transcriptional profiling to identify genes encoding signaling molecules that are differentially expressed in mature alpha/beta and gamma/delta T cell populations. Unexpectedly, we found that B lymphoid kinase (Blk), a Src family kinase expressed primarily in B cells, is expressed in gamma/delta T cells but not in alpha/beta T cells. Analysis of Blk-deficient mice revealed that Blk is required for the development of IL-17-producing gamma/delta T cells. Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny. Naive alpha/beta and gamma/delta T cells isolated from mouse lymph nodes and purified by negative selection were compared using MOE430 2.0 GeneChip.