Human CXCR5+CD45RA-CD8+ T cells subset in follicular lymphoma
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ABSTRACT:
PROVIDER: PRJNA414624 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6182760_1.fastq.gz | Fastqsanger.gz | |||
| SRR6182760_2.fastq.gz | Fastqsanger.gz | |||
| SRR6182761_1.fastq.gz | Fastqsanger.gz | |||
| SRR6182761_2.fastq.gz | Fastqsanger.gz | |||
| SRR6182756_1.fastq.gz | Fastqsanger.gz |
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Project description:We demonstrate that CXCR5+CD8+ T cells are a distinct human T-cell subset that homes to follicles and exerts strong antitumor activity compared with CXCR5-CD8+ T cells. Importantly, this subset is associated with improved outcome in follicular lymphoma patients.
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Project description:CD4+ T-cells from three follicular lymphoma tumors were sorted by flow cytometry into three subsets based on high (hi), intermediate (int), or low (lo) levels of PD-1 and CXCR5 expression and whole genome gene expression profiling was performed.
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Project description:In mice chronically infected with lymphocytic choriomeningitis virus (LCMV), we defined a subset of exhausted CD8+ T cells abundantly expressing chemokine receptor CXCR5. These CXCR5+ CD8+ T cells were preferentially localized in B cell follicles, expressing less inhibitory receptors while exhibiting more potent cytolytic activity compared to the CXCR5- subset. Furthermore, we identified Id2-E2A axis as the regulator for the generation of this subset. In line with mouse LCMV chronic infection, we also identified a CXCR5+ CD8+ T cell subset in human HIV patients, which negatively correlated with viral load. Moreover, when adoptively transferred to chronically infected recipients, CXCR5+ subset showed greater therapeutic potential than CXCR5- subset.
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Project description:CD4+ T-cells from three follicular lymphoma tumors were sorted by flow cytometry into three subsets based on high (hi), intermediate (int), or low (lo) levels of PD-1 and CXCR5 expression and whole genome gene expression profiling was performed. This set contains three samples for PD-1hiCXCR5hiCD4+ T cells, two samples for PD-1intCXCR5intCD4+ T cells, and three samples for PD-1loCXCR5loCD4+ T cells.
2013-11-21 | E-GEOD-52561 | biostudies-arrayexpress
Project description:The vast majority of currently licensed human vaccines work on the basis of long-term protective antibody responses. Generation of long term humoral immunity is a complex process predominantly dependent on germinal centers and CD4 T cell help to B cells. Follicular helper T cells (Tfh) are the specialized CD4 T cells for B cell help. However, whether such cells develop memory in humans and can be tracked in human blood has been enigmatic. We identified a subpopulation of blood CXCR5+ PD-1+CXCR3- resting CD4 T cells that are most related to Tfh cells of lymphoid tissue by gene expression profile and phenotype. Functional analysis showed that these memory Tfh cells were specialized for helping B cells. Moreover, these cells correlate with a clinically important outcome: development of potent neutralizing antibodies against HIV in HIV+ individuals. CD4 T cells were enriched from fresh blood of 5 normal donors by magnetic beads negative selection. Following enrichment, CD14-CD16-CD19-CD8-CD4+CD45RA- cells from each donor were FACS sorted into the following 5 populations: CXCR5-, CXCR5+PD1+CXCR3-, CXCR5+PD1+CXCR3+, CXCR5+PD1-CXCR3-, and CXCR5+PD1-CXCR3+. The gene expression profile of each cell population was determined.
2013-11-12 | E-GEOD-50390 | biostudies-arrayexpress
Project description:CXCR5 Antagonist in Angioimmunoblastic T-cell Lymphoma
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Project description:In response to infection, antigen-specific CD8+ T cells are primed in the T cell zone of secondary lymphoid organs and differentiate into cytotoxic effector T (TC) cells. Concurrently, CD4+ T cells differentiate into follicular helper T (TFH) cells that localize to B cell follicles and promote protective antibody responses. During unresolved infections, however, some viruses including human immunodeficiency virus (HIV) or Epsteinâ??Barr virus (EBV) escape immune control and persist in TFH cells and B cells, respectively. Exclusion of Tc cells from B cell follicles is thought to be a major mechanism of immune evasion. New strategies are therefore needed to eradicate infected cells in follicles for a permanent cure. Using mouse infection models and human samples, we here identify a specialized group of TC cells expressing the chemokine receptor CXCR5 that can selectively enter B cell follicles and eradicate infected TFH and B cells. We demonstrate that differentiation of these cells, which we term follicular cytotoxic T (TFC) cells, requires the transcription factors Bcl6, E2A and Tcf1, whereas the transcriptional regulators Blimp1, Id3 and Id2 inhibit their development. We demonstrate that Blimp1 and E2A directly regulate Cxcr5 expression, and together with Bcl6 and Tcf1 form a transcriptional circuit that guides the TFC differentiation. The identification of a follicular subset of TC cells has far reaching implications for developing better strategies for the control of infections that target B cells and TFH cells and for the eradication of B cell derived malignancies. There is no associated input. The E2A Bio-ChIP-seq was performed with total thymocytes from Tcf3Bio/Bio Rosa26BirA/BirA mice
2016-08-01 | E-GEOD-84974 | biostudies-arrayexpress
Project description:Follicular lymphoma is the most common indolent non-Hodgkin's lymphoma involving germinal centre B cells, with a subset of patients undergoing transformation to a diffuse large B-cell lymphoma (DLBCL) morphology for which the clinical outcomes are poor. To elucidate the differences in copy number profiles between FL and tFL groups, we performed Affymetrix SNP 6.0 Array analysis on 31 paired FL-tFL cases. We wanted to identify and compare recurrent somatic copy number alterations (CNAs) between the two groups (FL vs. tFL). In addition, the concordance and discordance in the copy neutral loss of heterozygosity (cnLOH) between the two groups were also investigated to identify recurrent target gene regions. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from follicular lymphoma (FL), transformed follicular lymphoma (tFL) and matching germline (GL) sample (if available). Copy number analysis of Affymetrix SNP 6.0 Array were performed on 91 DNA samples, consisting of 31 patients. Among the 31 patients, 19 had matching germline samples, while 12 had no germline samples. The Log R Ratio (LRR) values and the B Allele Frequency (BAF) values were subsequently calculated to search for copy number aberrations and copy neutral (CN)-LOH in the FL and tFL samples. Paired and unpaired analyses were performed accordingly.
2013-10-01 | E-GEOD-42525 | biostudies-arrayexpress
Project description:In response to infection, antigen-specific CD8+ T cells are primed in the T cell zone of secondary lymphoid organs and differentiate into cytotoxic effector T (TC) cells. Concurrently, CD4+ T cells differentiate into follicular helper T (TFH) cells that localize to B cell follicles and promote protective antibody responses. During unresolved infections, however, some viruses including human immunodeficiency virus (HIV) or Epstein–Barr virus (EBV) escape immune control and persist in TFH cells and B cells, respectively. Exclusion of Tc cells from B cell follicles is thought to be a major mechanism of immune evasion. New strategies are therefore needed to eradicate infected cells in follicles for a permanent cure. Using mouse infection models and human samples, we here identify a specialized group of TC cells expressing the chemokine receptor CXCR5 that can selectively enter B cell follicles and eradicate infected TFH and B cells. We demonstrate that differentiation of these cells, which we term follicular cytotoxic T (TFC) cells, requires the transcription factors Bcl6, E2A and Tcf1, whereas the transcriptional regulators Blimp1, Id3 and Id2 inhibit their development. We demonstrate that Blimp1 and E2A directly regulate Cxcr5 expression, and together with Bcl6 and Tcf1 form a transcriptional circuit that guides the TFC differentiation. The identification of a follicular subset of TC cells has far reaching implications for developing better strategies for the control of infections that target B cells and TFH cells and for the eradication of B cell derived malignancies. There is no associated input.
2016-08-01 | GSE84974 | GEO