Vaccine-induced ICOS+CD38+ cTfh are sensitive biosensors of age-related changes in inflammatory pathways
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE134416 | GEO | 2019/10/01
REPOSITORIES: GEO
Similar Datasets
Project description:Humoral immune responses are dysregulated with aging, but the cellular and molecular pathways involved remain incompletely understood. In particular, little is known about the effects of aging on T follicular helper (Tfh) CD4 cells, the key cells that provide help to B cells for effective humoral immunity. We performed transcriptional profiling and cellular analysis on circulating Tfh before and after influenza vaccination in young and elderly adults. First, whole-blood transcriptional profiling shows that ICOS+CD38+ cTfh following vaccination preferentially enriches in gene sets associated with youth versus aging compared to other circulating T cell types. Second, vaccine-induced ICOS+CD38+ cTfh from the elderly had increased the expression of genes associated with inflammation, including tumor necrosis factor-nuclear factor κB (TNF-NF-κB) pathway activation. Finally, vaccine-induced ICOS+CD38+ cTfh display strong enrichment for signatures of underlying age-associated biological changes. These data highlight the ability to use vaccine-induced cTfh as cellular "biosensors" of underlying inflammatory and/or overall immune health.
| S-EPMC8149371 | biostudies-literature
Project description:People living with HIV (PWH) often exhibit poor responses to influenza vaccination despite effective combination anti-retroviral (ART) mediated viral suppression. There exists a paucity of data in identifying immune correlates of influenza vaccine response in context of HIV infection that would be useful in improving its efficacy in PWH, especially in younger individuals. Transcriptomic data were obtained by microarray from whole blood isolated from aviremic pediatric and adolescent HIV-infected individuals (4-25 yrs) given two doses of Novartis/H1N1 09 vaccine during the pandemic H1N1 influenza outbreak. Supervised clustering and gene set enrichment identified contrasts between individuals exhibiting high and low antibody responses to vaccination. High responders exhibited hemagglutination inhibition antibody titers >1:40 post-first dose and 4-fold increase over baseline. Baseline molecular profiles indicated increased gene expression in metabolic stress pathways in low responders compared to high responders. Inflammation-related and interferon-inducible gene expression pathways were higher in low responders 3 wks post-vaccination. The broad age range and developmental stage of participants in this study prompted additional analysis by age group (e.g. <13yrs and >13yrs). This analysis revealed differential enrichment of gene pathways before and after vaccination in the two age groups. Notably, CXCR5, a homing marker expressed on T follicular helper (Tfh) cells, was enriched in high responders (>13yrs) following vaccination which was accompanied by peripheral Tfh expansion. Our results comprise a valuable resource of immune correlates of vaccine response to pandemic influenza in HIV infected children that may be used to identify favorable targets for improved vaccine design in different age groups.
2021-03-18 | GSE167893 | GEO
Project description:Vaccine-induced ICOS+CD38+ cTfh are sensitive biosensors of age-related changes in inflammatory pathways
| PRJNA555109 | ENA
Project description:COVID-19 mRNA vaccines generate high concentrations of circulating anti-Spike antibodies and Spike-specific CD4+ T cells following prime-boost vaccination. It is not yet clear if vaccine-induced CD4+ T cell responses in the draining lymph node contribute to this outstanding immunogenicity. Using fine needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we found large populations of Spike-specific CD4+ T follicular helper cells in the draining lymph node. A broadly immunodominant HLA-DPB1*04-restricted response to Spike166-180 composes one of the largest populations of T follicular helper cells in individuals with this allele, which is itself among the most common HLA alleles in the human population. Spike-specific T follicular helper cells are present in the lymph node 30 days after vaccine boost and persist in some individuals more than 170 days. Collectively, our results underscore the key role that robust T follicular helper cell responses play in the establishment of long-term immunity in this very efficacious human vaccine.
2022-01-04 | GSE183393 | GEO
Project description:Anti-PD-1 (aPD1) immunotherapy likely affects other immune cells including follicular helper CD4 T cells (Tfh) involved in germinal center (GC) responses. Little is known, however, about the effects of anti-PD-1 immunotherapy on non-cancer immune responses in humans. To investigate this question, we examined the impact of aPD1 immunotherapy for cancer on the Tfh-B cell axis responding to unrelated viral antigens. Following influenza vaccination, a subset of adults receiving aPD1 had more robust circulating Tfh (cTfh) responses than adults not receiving immunotherapy, and cTfh responses correlated with plasmablasts. PD-1 pathway blockade also resulted in transcriptional signatures of increased cellular proliferation in cTfh and responding B cells compared to controls.
2022-06-01 | GSE179487 | GEO
Project description:Systems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology. Here we used the systems vaccinology approach to study the molecular mechanisms underlying the innate responses to the trivalent inactivated influenza (TIV) and live attenuated influenza (LAIV) vaccination in humans, and to identify early gene signatures that predict the magnitude of the antibody responses to influenza vaccination. During the 2008 influenza season, healthy adults were vaccinated with LAIV (28 vaccinees), and blood samples isolated at days 0, 3, 7 post-vaccination. Microarrays were performed using total RNA extracted from the peripheral blood mononuclear cells of vaccinees.
2011-07-10 | E-GEOD-29615 | biostudies-arrayexpress
Project description:Systems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology. Here we used the systems vaccinology approach to study the molecular mechanisms underlying the innate responses to the trivalent inactivated influenza (TIV) and live attenuated influenza (LAIV) vaccination in humans, and to identify early gene signatures that predict the magnitude of the antibody responses to influenza vaccination. During the 2008 influenza season, healthy adults were vaccinated with TIV (28 vaccinees), and blood samples isolated at days 0, 3, 7 post-vaccination. Microarrays were performed using total RNA extracted from the peripheral blood mononuclear cells of vaccinees.
2011-07-10 | E-GEOD-29617 | biostudies-arrayexpress
Project description:Systems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology. Here we used the systems vaccinology approach to study the molecular mechanisms underlying the innate responses to the trivalent inactivated influenza (TIV) and live attenuated influenza (LAIV) vaccination in humans, and to identify early gene signatures that predict the magnitude of the antibody responses to influenza vaccination. During the 2007 Influenza season, healthy adults were vaccinated with TIV (9 vaccinees), and blood samples isolated at days 0, 3, 7 post-vaccination. Microarrays were performed using total RNA extracted from the peripheral blood mononuclear cells of vaccinees.
2011-07-10 | E-GEOD-29614 | biostudies-arrayexpress
Project description:Virus infection induces T follicular helper (TFH) and T helper 1 (TH1) cells. Although TFH cells are important in anti-viral humoral immunity, the role of TH 1 cells is still elusive. IgG2 antibodies predominate in the response to vaccination with inactivated Influenza A virus (IAV) and were responsible for protective immunity to lethal challenge with pathogenic H5N1 and pandemic H1N1 IAVs even in mice lacking TFH cells owing to B or T cell-specific ablation of the Bcl6. We demonstrate that IL-21 and IFN-γ secreted from TH1 cells were essential for greater persistence and higher titers of IgG2 protective antibodies. These results suggest that TH1 induction could be a promising strategy to induce effective neutralizing antibodies against emerging influenza viruses.
2016-10-12 | GSE85316 | GEO