Naive and memory CD4+ T cell subsets can contribute to the generation of human Tfh cells

Raphaël Jeger-Madiot; Romain Vaineau; Maud Heredia; Nicolas Tchitchek; Lisa Bertrand; Mathias Pereira; Océane Konza; Bruno Gouritin; Bénédicte Hoareau-Coudert; Aurélien Corneau; Catherine Blanc; Eric Savier; Pierre Buffet; Adrien Six; David Klatzmann; Arnaud Moris; Stéphanie Graff-Dubois

doi:10.1016/j.isci.2021.103566

Naive and memory CD4⁺ T cell subsets can contribute to the generation of human Tfh cells

iScience. 2021 Dec 3;25(1):103566. doi: 10.1016/j.isci.2021.103566. eCollection 2022 Jan 21.

Authors

Raphaël Jeger-Madiot^{1

2}, Romain Vaineau¹, Maud Heredia^{1

2}, Nicolas Tchitchek¹, Lisa Bertrand^{2

3}, Mathias Pereira^{2

3}, Océane Konza¹, Bruno Gouritin¹, Bénédicte Hoareau-Coudert⁴, Aurélien Corneau⁴, Catherine Blanc⁴, Eric Savier^{5

6}, Pierre Buffet⁷, Adrien Six^{1

8}, David Klatzmann^{1

8}, Arnaud Moris^{2

3}, Stéphanie Graff-Dubois^{1

2

4

5}

Affiliations

¹ Sorbonne Université, INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Paris, France.
² Sorbonne Université, INSERM, CNRS, Center for Immunology and Microbial Infections, Paris, France.
³ Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell, Gif-sur-Yvette, France.
⁴ Sorbonne Université, INSERM UMS037 PASS, Cytometry facility (CyPS), Paris, France.
⁵ Assistance Publique-Hôpitaux de Paris (AP-HP), Pitie-Salpetriere Hospital, Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Paris, France.
⁶ Sorbonne Université, INSERM, St Antoine Research Center CRSA, Paris, France.
⁷ Université de Paris, INSERM, UMRS 1134, Biologie Intégrée du Globule Rouge, Paris, France.
⁸ Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Biotherapy and Département Hospitalo-Universitaire Inflammation-Immunopathology-Biotherapy (i2B), Paris, France.

Abstract

CD4⁺ T follicular helper cells (Tfh) promote B cell maturation and antibody production in secondary lymphoid organs. By using an innovative culture system based on splenocyte stimulation, we studied the dynamics of naive and memory CD4⁺ T cells during the generation of a Tfh cell response. We found that both naive and memory CD4⁺ T cells can acquire phenotypic and functional features of Tfh cells. Moreover, we show here that the transition of memory as well as naive CD4⁺ T cells into the Tfh cell profile is supported by the expression of pro-Tfh genes, including transcription factors known to orchestrate Tfh cell development. Using this culture system, we provide pieces of evidence that HIV infection differentially alters these newly identified pathways of Tfh cell generation. Such diversity in pathways of Tfh cell generation offers a new framework for the understanding of Tfh cell responses in physiological and pathological contexts.

Keywords: Cell biology; Immunology; Virology.