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
Affiliations
Raphaël Jeger-Madiot
Sorbonne Université, INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Paris, France; Sorbonne Université, INSERM, CNRS, Center for Immunology and Microbial Infections, Paris, France
Romain Vaineau
Sorbonne Université, INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Paris, France
Maud Heredia
Sorbonne Université, INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Paris, France; Sorbonne Université, INSERM, CNRS, Center for Immunology and Microbial Infections, Paris, France
Nicolas Tchitchek
Sorbonne Université, INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Paris, France
Lisa Bertrand
Sorbonne Université, INSERM, CNRS, Center for Immunology and Microbial Infections, Paris, France; Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell, Gif-sur-Yvette, France
Mathias Pereira
Sorbonne Université, INSERM, CNRS, Center for Immunology and Microbial Infections, Paris, France; Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell, Gif-sur-Yvette, France
Océane Konza
Sorbonne Université, INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Paris, France
Bruno Gouritin
Sorbonne Université, INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Paris, France
Bénédicte Hoareau-Coudert
Sorbonne Université, INSERM UMS037 PASS, Cytometry facility (CyPS), Paris, France
Aurélien Corneau
Sorbonne Université, INSERM UMS037 PASS, Cytometry facility (CyPS), Paris, France
Catherine Blanc
Sorbonne Université, INSERM UMS037 PASS, Cytometry facility (CyPS), Paris, France
Eric Savier
Assistance Publique-Hôpitaux de Paris (AP-HP), Pitie-Salpetriere Hospital, Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Paris, France; Sorbonne Université, INSERM, St Antoine Research Center CRSA, Paris, France
Pierre Buffet
Université de Paris, INSERM, UMRS 1134, Biologie Intégrée du Globule Rouge, Paris, France
Adrien Six
Sorbonne Université, INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Paris, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Biotherapy and Département Hospitalo-Universitaire Inflammation-Immunopathology-Biotherapy (i2B), Paris, France
David Klatzmann
Sorbonne Université, INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Paris, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Biotherapy and Département Hospitalo-Universitaire Inflammation-Immunopathology-Biotherapy (i2B), Paris, France
Arnaud Moris
Sorbonne Université, INSERM, CNRS, Center for Immunology and Microbial Infections, Paris, France; Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell, Gif-sur-Yvette, France
Stéphanie Graff-Dubois
Sorbonne Université, INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Paris, France; Sorbonne Université, INSERM, CNRS, Center for Immunology and Microbial Infections, Paris, France; Sorbonne Université, INSERM UMS037 PASS, Cytometry facility (CyPS), Paris, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Pitie-Salpetriere Hospital, Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Paris, France; Correspondance
Summary: 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.
