Noncanonical functions of T follicular helper cells

Shivangi Dave; André Ballesteros-Tato

doi:10.1126/sciimmunol.adr1052

journal article Jun 13, 2025

Noncanonical functions of T follicular helper cells

Shivangi Dave

André Ballesteros-Tato

Science Immunology Vol. 10 No. 108 · American Association for the Advancement of Science (AAAS)

View at Publisher Save 10.1126/sciimmunol.adr1052

Abstract

T follicular helper cells (T
FH
cells) are essential for germinal center (GC) formation and maintenance. However, recent insights reveal that T
FH
cells play additional immune regulatory roles beyond their traditional B cell helper function. Here, we review the functional and anatomical diversity of T
FH
cells and their unconventional roles in modulating immune responses during infection, vaccination, allergy, and tolerance. These functions include their stem-like memory T cell properties and their role as reservoirs for effector T cell (T
eff
cell) precursors. We also summarize the contributions of “ex-T
FH
cells” to immune homeostasis and the functions of diverse subsets of cytokine-producing T
FH
cells in aiding CD8
+
T cells and regulating critical B cell fate decisions. In summary, this Review underscores the multifaceted contributions of T
FH
cells to immune regulation, extending beyond their traditional B cell helper roles.

Topics

No keywords indexed for this article. Browse by subject →

References

158

[1]

10.4049/jimmunol.179.8.5099

[2]

10.1084/jem.192.11.1545

[3]

T Follicular Helper Cell Biology: A Decade of Discovery and Diseases

Shane Crotty

Immunity 10.1016/j.immuni.2019.04.011

[4]

Germinal Centers

Gabriel D. Victora, Michel C. Nussenzweig

Annual Review of Immunology 10.1146/annurev-immunol-120419-022408

[5]

10.1038/s41577-020-00446-2

[6]

10.1111/imr.12934

[7]

10.1126/science.1175870

[8]

10.1126/science.1176676

[9]

10.1016/j.immuni.2009.07.002

[10]

10.1038/s41423-020-00554-y

[11]

10.1016/j.immuni.2011.03.023

[12]

10.4049/jimmunol.1101393

[13]

10.1016/j.immuni.2011.03.024

[14]

10.1038/nature07345

[15]

10.1016/j.immuni.2010.07.015

[16]

Migratory CD11b + conventional dendritic cells induce T follicular helper cell–dependent antibody responses

Jayendra Kumar Krishnaswamy, Uthaman Gowthaman, Biyan Zhang et al.

Science Immunology 10.1126/sciimmunol.aam9169

[17]

10.1016/j.alit.2021.01.008

[18]

10.3389/fimmu.2018.02169

[19]

10.1038/nature17947

[20]

10.1371/journal.pone.0017739

[21]

10.1126/sciimmunol.aaw7636

[22]

10.4049/jimmunol.1203032

[23]

10.1084/jem.20150402

[24]

10.1016/j.immuni.2012.02.012

[25]

10.1084/jem.20111174

[26]

10.1038/nature12058

[27]

10.1016/j.immuni.2018.06.012

[28]

10.1016/j.immuni.2015.03.002

[29]

10.1084/jem.20131666

[30]

10.1038/nature13803

[31]

10.1084/jem.20091738

[32]

10.1016/j.immuni.2012.11.020

[33]

10.1038/s41590-024-01882-1

[34]

10.1016/j.immuni.2015.11.017

[35]

10.1038/s41590-024-01860-7

[36]

10.1084/jem.20232015

[37]

Long-lived T follicular helper cells retain plasticity and help sustain humoral immunity

Marco Künzli, David Schreiner, Tamara C. Pereboom et al.

Science Immunology 10.1126/sciimmunol.aay5552

[38]

10.1016/j.immuni.2013.02.020

[39]

10.1002/eji.201242540

[40]

10.1016/j.jaut.2018.09.001

[41]

10.1038/ni.2261

[42]

10.1016/j.immuni.2023.08.015

[43]

10.1016/j.immuni.2024.11.006

[44]

10.1126/science.aaw6433

[45]

10.1038/ni.3788

[46]

10.1084/jem.20170457

[47]

10.1084/jem.20102065

[48]

10.1016/j.immuni.2021.08.028

[49]

10.1016/j.immuni.2022.01.002

[50]

L. Shehata C. D. Thouvenel B. D. Hondowicz L. A. Pew D. J. Rawlings J. Choi M. Pepper IL-4 downregulates BCL6 to promote memory B cell selection in germinal centers. bioRxiv 525749 [Preprint] (2023). https://doi.org/10.1101/2023.01.26.525749. 10.1101/2023.01.26.525749

Showing 50 of 158 references

Metrics

9

Citations

158

References

Details

Published: Jun 13, 2025
Vol/Issue: 10(108)

Authors

S

Shivangi Dave

Adaptative Immunity and Immunoregulation Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

A

André Ballesteros-Tato

Adaptative Immunity and Immunoregulation Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

Cite This Article

Shivangi Dave, André Ballesteros-Tato (2025). Noncanonical functions of T follicular helper cells. Science Immunology, 10(108). https://doi.org/10.1126/sciimmunol.adr1052

Noncanonical functions of T follicular helper cells

You May Also Like