Project description:Human T-cells that express CXCR5 and/or CCR6 provide help to naive B-cells for IgG production. To understand the molecular pathways that are shared or unique to individual B helper T-cell subsets in human peripheral blood, CD4+IL-7R+CD25-/lo helper T-cells were purified according to the expression of CXCR5, CCR6, CXCR3, CD161 and CCR5 as follows: 1) TFH17(CD161-): CXCR5+CXCR6+CXCR3-CD161- 2) Th17: CXCR5-CCR6+CXCR3-, CD161+ or CCR5+ 3) CCR6”SP”: CXCR5-CCR6+CXCR3-CD161-CCR5- RNA-seq was performed with FACS-purified T-cell subsets from 3 healthy individuals.
Project description:Regulatory T cells (Treg) are a cornerstone of immune regulation. Recent evidence indicates that human Treg show plasticity in specific settings. A subpopulation of Treg expressing CD161, a marker associated with T helper (Th)17 cells, have T effector -like characteristics and are enriched at sites of autoimmune inflammation. Here we used RNAseq to confirm the effector-like signature of CD161+ Treg and demonstrated a shared transcriptional signature between CD161+ Treg and CD161+ conventional T cells (Tconv). Pathway analysis suggested that CD161+ T cells have a migratory phenotype, expressing high levels of CCR9 and integrin α4β7, markers associated with gut homing. In response to all-trans retinoic acid, CD161+ T cells expressed higher levels of CCR9 and integrin α4β7 than CD161- T cells. Our data suggest that blood CD161+ T cells may have adopted gut homing properties upon retinoic acid exposure. In contrast to their peripheral counterparts, CD161+ T cells from the site of autoimmune arthritis have a diminished gut homing phenotype and blunted response to retinoic acid. In health, the TCRβ repertoires of CD161+ and CD161- T cells showed limited overlap whereas there is clear overlap in T cell clones from synovial fluid of autoimmune arthritis patients. We therefore propose that CD161+ and CD161- T cells are largely distinct populations in the healthy immune system but that the inflamed site creates an environment where CD161 levels in T cells can be altered, potentially contributing to disease pathogenesis.
Project description:Human CD4 T cells from the colonic lamina propria were sorted based on the expression of CD161 and CD56. CD161hiCD56-, CD161hiCD56+, CD161int and CD161- CD4 T cells were compared to each other.
Project description:T lymphocytes are conventionally divided into subsets based upon expression of co-receptors, cytokines and surface molecules. By mRNA microarray analysis, T lymphocytes that express the C-type lectin CD161 were identified to share a transcriptional profile, which led to the identification of an innate function across these previously defined subsets, including CD8, CD4 and TCRgd T cells. Gene expression of magnetically enriched, resting CD161+ and CD161- CD4+ T cells from peripheral blood was measured in 3 healthy donors.
Project description:In this study, we examined differential gene expression in naïve human CD4+ T cells, as well as in effector Th1, Th17-negative and Th17-enriched CD4- T cell subsets. We observed a marked enrichment for increased gene expression in effector CD4+ T cells compared to naive CD4+ among immune-mediated disease oci genes. Within effector T cells, expression of disease-associated genes was increased in Th17-enriched compared to Th17-negative cells. We used microarray to examine the gene expresssion profile and level of human naïve, Th1 and effector T cell subsets. Human PBMCs were isolated and sorted to naïve, CD161-CCR6- and CD161+CCR6+ memory T cells. Naïve T cells were differentiatied to Th1 cells, and CD161-CCR6- and CD161+CCR6+ memory T cells were in vitro expanded for Th17-negative and Th17-enriched effector T cells. The gene profile was compared among naive, Th1, Th17-negative, and Th17-enriched cell subsets.
Project description:T lymphocytes are conventionally divided into subsets based upon expression of co-receptors, cytokines and surface molecules. By mRNA microarray analysis, T lymphocytes that express the C-type lectin CD161 were identified to share a transcriptional profile, which led to the identification of an innate function across these previously defined subsets, including CD8, CD4 and TCRgd T cells. Gene expression of sort purified, resting CD161++, CD161+ and CD161- CD8+ T cells from peripheral blood was measured in 4 healthy donors.
Project description:T lymphocytes are conventionally divided into subsets based upon expression of co-receptors, cytokines and surface molecules. By mRNA microarray analysis, T lymphocytes that express the C-type lectin CD161 were identified to share a transcriptional profile, which led to the identification of an innate function across these previously defined subsets, including CD8, CD4 and TCRgd T cells. Gene expression of sort purified, resting CD161+ and CD161- TCRgd T cells from peripheral blood was measured in 4 healthy donors.
