ArticleJCI insight2019
Follicular regulatory T cells inhibit the development of granzyme B-expressing follicular helper T cells.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- TGF-β and IL-2 differentially shape T follicular regulatory cell differentiation and stability in vitro.Cellular & molecular immunology · 2026Article
- Tfh2 and a subset of Tfh1 cells associate with antibody-mediated immunity to malaria.JCI insight · 2025Article
- T follicular helper cell development during malaria.Current opinion in immunology · 2025Review
- The T follicular helper/T follicular helper regulatory pathway in FVIII immune responses in mice.Blood · 2025Article
- LAG3 regulates antibody responses in a murine model of kidney transplantation.The Journal of clinical investigation · 2025Article
- Follicular helper T cells (Tfh): heterogeneity in spatial distribution and phenotypic characteristics.Frontiers in immunology · 2025Review
- T follicular regulatory cells in food allergy promote IgE via IL-4.JCI insight · 2024Article
- COVID-19: from immune response to clinical intervention.Precision clinical medicine · 2024Review
- Function of unconventional T cells in oral lichen planus revealed by single-cell RNA sequencing.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Oligoclonal CD4Communications biology · 2024Article
- Article
- Tertiary lymphoid structures sustain cutaneous B cell activity in hidradenitis suppurativa.JCI insight · 2024Article
- Epigenetic regulation of human FOXP3+ Tregs: from homeostasis maintenance to pathogen defense.Frontiers in immunology · 2024Review
- Immunotherapy-induced cytotoxic T follicular helper cells reduce numbers of retrovirus-infected reservoir cells in B cell follicles.PLoS pathogens · 2023Article
- Interactions between B cells and T follicular regulatory cells enhance susceptibility to Brucella infection independent of the anti-Brucella humoral response.PLoS pathogens · 2023Article
- Cytotoxic peripheral T-cell lymphomas and EBV-positive T/NK-cell lymphoproliferative diseases: emerging concepts, recent advances, and the putative role of clonal hematopoiesis. A report of the 2022 EA4HP/SH lymphoma workshop.Virchows Archiv : an international journal of pathology · 2023Article
- Diphtheria toxin-derived, anti-PD-1 immunotoxin, a potent and practical tool to selectively deplete PD-1Protein science : a publication of the Protein Society · 2023Article
- CTLA4 protects against maladaptive cytotoxicity during the differentiation of effector and follicular CD4Cellular & molecular immunology · 2023Article
- ICOS costimulation is indispensable for the differentiation of T follicular regulatory cells.Life science alliance · 2023Article
- Lymphocyte Subpopulations Associated with Neutralizing Antibody Levels of SARS-CoV-2 for COVID-19 Vaccination.Vaccines · 2022Article
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Authors and funding
6 authors.
Funding
Abstract
T follicular regulatory (TFR) cells are found in the germinal center (GC) response and help shape the antibody (Ab) response. However, the precise role of TFR cells in the GC is controversial. Here, we addressed TFR cell function using mice with impaired TFR cell development (Bcl6-flox/Foxp3-cre, or Bcl6FC mice), mice with augmented TFR cell development (Blimp1-flox/Foxp3-cre, or Blimp1FC mice), and two different methods of immunization. Unexpectedly, GC B cell levels positively correlated with TFR cell levels. Using a gene profiling approach, we found that TFH cells from TFR-deficient mice showed strong upregulation of granzyme B (Gzmb) and other effector CD8+ T cell genes, many of which were Stat4 dependent. The upregulation of cytotoxic genes was the highest in TFH cells from TFR-deficient mice where Blimp1 was also deleted in Foxp3+ regulatory T cells (Bcl6-flox/Prdm1-flox/Foxp3-cre [DKO] mice). Granzyme B- and Eomesodermin-expressing TFH cells correlated with a higher rate of apoptotic GC B cells. Klrg1+ TFH cells from DKO mice expressed higher levels of Gzmb. Our data show that TFR cells repress the development of abnormal cytotoxic TFH cells, and the presence of cytotoxic TFH cells correlates with a lower GC and Ab response. Our data show what we believe is a novel mechanism of action for TFR cells helping the GC response.
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