Blood PD-1+ CXCR3- CXCR5+ CD4 T cells and active GC Tfh cells share a transcriptional profile signature
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE50392 | GEO | 2013/11/12
SECONDARY ACCESSION(S): PRJNA217398
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-11-12 | E-GEOD-50392 | biostudies-arrayexpress
Project description:Blood PD-1+ CXCR3- CXCR5+ CD4 T cells and active GC Tfh cells share a transcriptional profile signature
| PRJNA217398 | ENA
Project description:The vast majority of currently licensed human vaccines work on the basis of long-term protective antibody responses. It is now conceivable that an antibody-dependent HIV vaccine might be possible, given the discovery of HIV broadly neutralizing antibodies (bnAbs) in some HIV-infected individuals. However, these antibodies are difficult to develop and have characteristics indicative of a high degree of affinity maturation in germinal centers (GCs). CD4? T follicular helper (Tfh) cells are specialized for B cell help and necessary for GCs. Therefore, the development of HIV bnAbs might depend on Tfh cells. Here, we identified in normal individuals a subpopulation of circulating memory PD-1?CXCR5?CD4? T cells that are resting memory cells most related to bona fide GC Tfh cells by gene expression profile, cytokine profile, and functional properties. Importantly, the frequency of these cells correlated with the development of bnAbs against HIV in a large cohort of HIV? individuals.
| S-EPMC3996844 | biostudies-literature
Project description:HIV-1-specific broadly neutralizing antibodies (bnAbs) typically develop in individuals with continuous high-level viral replication and increased immune activation, conditions that cannot be reproduced during prophylactic immunization. Understanding mechanisms supporting bnAb development in the absence of high-level viremia may be important for designing bnAb-inducing immunogens. Here, we show that the breadth of neutralizing antibody responses in HIV-1 controllers was associated with a relative enrichment of circulating CXCR5+CXCR3+PD-1lo CD4+ T cells. These CXCR3+PD-1lo Tfh-like cells were preferentially induced in vitro by functionally superior dendritic cells from controller neutralizers, and able to secrete IL-21 and support B cells. In addition, these CXCR3+PD-1lo Tfh-like cells contained higher proportions of stem cell-like memory T cells, and upon antigenic stimulation differentiated into PD-1hi Tfh-like cells in a Notch-dependent manner. Together, these data suggest that CXCR5+CXCR3+PD-1lo cells represent a dendritic cell-primed precursor cell population for PD-1hi Tfh-like cells that may contribute to the generation of bnAbs in the absence of high-level viremia.
| S-EPMC5256133 | biostudies-literature
Project description:HIV-1-specific broadly-neutralizing antibodies (bnAb) typically develop in individuals with continuous high-level viral replication and increased immune activation, conditions that cannot be reproduced during prophylactic immunization. Understanding mechanisms supporting bnAb development in the absence of high-level viremia may be important for designing bnAb-inducing immunogens. Here, we show that the breadth of neutralizing antibody responses in HIV-1 controllers was associated with a relative enrichment of circulating CXCR5+ CXCR3+ PD-1Lo CD4 T cells. These CXCR3+ PD-1Lo Tfh-like cells were preferentially induced in vitro by functionally superior dendritic cells from controller neutralizers, and able to secrete IL-21 and support B cells. In addition, these CXCR3+ PD-1Lo Tfh-like cells contain higher proportions of stem cell-like memory T cells, and upon antigenic stimulation differentiated into PD-1Hi Tfh-like cells in a Notch-dependent manner. Together, these data suggest that CXCR5+ CXCR3+ PD-1Lo cells represent a dendritic cell-primed precursor cell population for PD-1Hi Tfh-like cells that may contribute to the generation of bnAbs in the absence of high–level viremia.
2017-02-01 | GSE90897 | GEO
Project description:After activation, CD4+ helper T (Th) cells differentiate; into distinct effector subsets. Although chemokine; (C-X-C motif) receptor 5-expressing T follicular; helper (Tfh) cells are important in humoral immunity,; their developmental regulation is unclear. Here we; show that Tfh cells had a distinct gene expression; profile and developed in vivo independently of the; Th1 or Th2 cell lineages. Tfh cell generation was regulated; by ICOS ligand (ICOSL) expressed on B cells; and was dependent on interleukin-21 (IL-21), IL-6,; and signal transducer and activator of transcription; 3. However, unlike Th17 cells, differentiation of Tfh; cells did not require transforming growth factor; b (TGF-b) or Th17-specific orphan nuclear receptors; RORa and RORg in vivo. Finally, naive T cells activated; in vitro in the presence of IL-21 but not; TGF-b signaling preferentially acquired Tfh gene; expression and promoted germinal-center reactions; in vivo. This study thus demonstrates that Tfh is a; distinct Th cell lineage. Experiment Overall Design: Splenic CD4+CXCR5+ T cells were isolated from KLH-immunized mice and restimulated with anti-CD3 for 4 hours before total RNA preparation. Affymetrix gene chips were used to analyze their gene expression.
2008-10-21 | E-GEOD-11924 | biostudies-arrayexpress
Project description:The goal of an HIV vaccine is to generate robust and durable protective Ab. Vital to this goal is the induction of CD4(+) T follicular helper (TFH) cells. However, very little is known about the TFH response to HIV vaccination and its relative contribution to magnitude and quality of vaccine-elicited Ab titers. In this study, we investigated these questions in the context of a DNA/modified vaccinia virus Ankara SIV vaccine with and without gp140 boost in aluminum hydroxide in rhesus macaques. In addition, we determined the frequency of vaccine-induced CD4(+) T cells coexpressing chemokine receptor, CXCR5 (facilitates migration to B cell follicles) in blood and whether these responses were representative of lymph node TFH responses. We show that booster modified vaccinia virus Ankara immunization induced a distinct and transient accumulation of proliferating CXCR5(+) and CXCR5(-) CD4 T cells in blood at day 7 postimmunization, and the frequency of the former but not the latter correlated with TFH and B cell responses in germinal centers of the lymph node. Interestingly, gp140 boost induced a skewing toward CXCR3 expression on germinal center TFH cells, which was strongly associated with longevity, avidity, and neutralization potential of vaccine-elicited Ab response. However, CXCR3(+) cells preferentially expressed the HIV coreceptor CCR5, and vaccine-induced CXCR3(+)CXCR5(+) cells showed a moderate positive association with peak viremia following SIV251 infection. Taken together, our findings demonstrate that vaccine regimens that elicit CXCR3-biased TFH cell responses favor Ab persistence and avidity but may predispose to higher acute viremia in the event of breakthrough infections.
| S-EPMC4506863 | biostudies-literature
Project description:Many autoimmune diseases are characterized by the production of autoantibodies. The current view is that CD4+ Tfh cells are the main subset regulating autoreactive B cells. Here, we discover a novel CXCR5+PD1+ Tfh subset of CD8+ T cells whose development and function are negatively regulated by Stat5. These CD8+ Tfh cells regulate the GC B cell response and control autoantibody production. Deficiency of Stat5 in CD8+ T cells leads to an increase of CD8+ Tfh cells, resulting in the breakdown of B cell tolerance and autoantibody production. CD8+ Tfh cells share similar gene signatures with CD4+ Tfh cells and require CD40L/CD40 and TCR/MHCI interactions to deliver help to B cells. Our study highlights the diversity of follicular T cell subsets that contribute to the breakdown of B-cell tolerance
2019-08-30 | GSE136640 | GEO
Project description:Seasonal influenza vaccine protects 60 to 90% of healthy young adults from influenza infection. The immunological events that lead to the induction of protective antibody responses remain poorly understood in humans. We identified the type of CD4+ T cells associated with protective antibody responses after seasonal influenza vaccinations. The administration of trivalent split-virus influenza vaccines induced a temporary increase of CD4+ T cells expressing ICOS, which peaked at day 7, as did plasmablasts. The induction of ICOS was largely restricted to CD4+ T cells coexpressing the chemokine receptors CXCR3 and CXCR5, a subpopulation of circulating memory T follicular helper cells. Up to 60% of these ICOS+CXCR3+CXCR5+CD4+ T cells were specific for influenza antigens and expressed interleukin-2 (IL-2), IL-10, IL-21, and interferon-? upon antigen stimulation. The increase of ICOS+CXCR3+CXCR5+CD4+ T cells in blood correlated with the increase of preexisting antibody titers, but not with the induction of primary antibody responses. Consistently, purified ICOS+CXCR3+CXCR5+CD4+ T cells efficiently induced memory B cells, but not naïve B cells, to differentiate into plasma cells that produce influenza-specific antibodies ex vivo. Thus, the emergence of blood ICOS+CXCR3+CXCR5+CD4+ T cells correlates with the development of protective antibody responses generated by memory B cells upon seasonal influenza vaccination.
| S-EPMC3621097 | biostudies-literature
Project description:How follicular T-helper (Tfh) cells develop is incompletely understood. We find that, upon antigen exposure in vivo, both naïve and antigen-experienced T cells sequentially upregulate CXCR5 and Bcl6 within the first 24 h, relocate to the T-B border, and give rise to phenotypic Bcl6(+)CXCR5(+) Tfh cells before the first cell division. CXCR5 upregulation is more dependent on ICOS costimulation than that of Bcl6, and early Bcl6 induction requires T-cell expression of CXCR5 and, presumably, relocation toward the follicle. This early and rapid upregulation of CXCR5 and Bcl6 depends on IL-6 produced by radiation-resistant cells. These results suggest that a Bcl6(hi)CXCR5(hi) phenotype does not automatically define a Tfh lineage but might reflect a state of antigen exposure and non-commitment to terminal effector fates and that niches in the T-B border and/or the follicle are important for optimal Bcl6 induction and maintenance.
| S-EPMC4624673 | biostudies-literature