Copyright: © 2025 by the authors. Licensee: Pirogov University.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (CC BY).

OPINION

Follicular T cells in peripheral blood: increasing complexity and key questions

About authors

The Russian National Research Medical University named after N.I.Pirogov, Moscow

Correspondence: Irina L. Grigorova
Ostrovityanova, 1, Moscow, 117997, Russia; moc.liamg@67girg

About paper

Funding: this research was supported by the Russian Science Foundation (Grant No. 24-15-00545).

Acknowledgments: the author is grateful to I. V. Zvyagin for assistance with editing the article.

Received: 2025-12-10 Accepted: 2025-12-12 Published online: 2025-12-23
|
  1. Ansel KM, McHeyzer-Williams LJ, Ngo VN, McHeyzer-Williams MG, Cyster JG. In vivo-activated CD4 T cells upregulate CXC chemokine receptor 5 and reprogram their response to lymphoid chemokines. J Exp Med. 1999; 190: 1123–34.
  2. Crotty S. T Follicular Helper Cell Biology: A Decade of Discovery and Diseases. Immunity. 2019; 50: 1132–48.
  3. Yu D, Walker LSK, Liu Z, Linterman MA, Li Z. Targeting TFH cells in human diseases and vaccination: rationale and practice. Nat Immunol. 2022; 23: 1157–68.
  4. Victora GD, Nussenzweig MC. Germinal Centers. Annu Rev Immunol. 2022; 40: 413–42.
  5. Sokolova S, Grigorova IL. Follicular regulatory T cell subsets in mice and humans: origins, antigen specificity and function. Int Immunol. 2023; dxad031.
  6. Le Coz C, Oldridge DA, Herati RS, De Luna N, Garifallou J, Cruz Cabrera E, et al. Human T follicular helper clones seed the germinal center-resident regulatory pool. Sci Immunol. 2023; 8: eade8162.
  7. Jacobsen JT, Hu W, R Castro TB, Solem S, Galante A, Lin Z, et al. Expression of Foxp3 by T follicular helper cells in end-stage germinal centers. Science. 2021; 373: eabe5146.
  8. Flores-Pérez PN, Collazo-Llera JA, Rodríguez-Alvarado FA, Rivera-Amill V. The Emerging Role of Circulating T Follicular Helper Cells in Dengue Virus Immunity: Balancing Protection and Pathogenesis. Viruses. 2025; 17: 652.
  9. Tulyeu J, Søndergaard JN, Priest DG, Ebihara T, Matsumoto H, Llamas-Covarrubias MA,et al. Human precursor T follicular regulatory cells are primed for differentiation into mature Tfr and disrupted during severe infections. Sci Adv. 2025; 11: eadv6939.
  10. Søndergaard JN, Tulyeu J, Edahiro R, Shirai Y, Yamaguchi Y, Murakami T, et al. A sex-biased imbalance between Tfr, Tph, and atypical B cells determines antibody responses in COVID-19 patients. Proc Natl Acad Sci USA. 2023; 120: e2217902120.
  11. Song W, Craft J. T Follicular Helper Cell Heterogeneity. Annual Review of Immunology. 2024; 42: 127–52.
  12. Gowthaman U, Chen JS, Zhang B, Flynn WF, Lu Y, Song W, et al. Identification of a T follicular helper cell subset that drives anaphylactic IgE. Science. 2019; 365: eaaw6433.
  13. Sage PT, Alvarez D, Godec J, von Andrian UH, Sharpe AH. Circulating T follicular regulatory and helper cells have memory-like properties. J Clin Invest. 2014; 124: 5191–204.
  14. Su R, Wang Y, Hu F, Li B, Guo Q, Zheng X, et al. Altered Distribution of Circulating T Follicular Helper-Like Cell Subsets in Rheumatoid Arthritis Patients. Front Med (Lausanne). 2021; 8: 690100.
  15. Jugder B-E, Park E, Du L, Jawale C, Popov N, Guo Z, et al. Tissue-specific roles of regulatory T cells: mechanisms of suppression and beyond along with emerging therapeutic insights in autoimmune indications. Front Immunol. 2025; 16: 1650451.