CXCR5+PD-1++ CD4+ T cells colonize infant intestines early in life and promote B cell maturation

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外文摘要：Gastrointestinal infections are a major cause for serious clinical complications in infants.The induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++ CD4+ T cells(TFH cells).We investigated the ontogeny of CXCR5+PD-1++ CD4+ T cells in human intestines.While CXCR5+PD-1++ CD4+ T cells were absent in fetal intestines,CXCR5+PD-1++ CD4+ T cells increased after birth and were abundant in infant intestines,resulting in significant higher numbers compared to adults.These findings were supported by scRNAseq analyses,showing increased frequencies of CD4+ T cells with a TFH gene signature in infant intestines compared to blood.Co-cultures of autologous infant intestinal CXCR5+PD-1+/-CD4+ T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B cells.Taken together,we demonstrate that functional TFH cells are numerous in infant intestines,making them a promising target for oral pediatric vaccine strategies.

外文关键词：

TFH cellsB cellsAntibodiesIntestinePediatrics

作者：

Ana Jordan-Paiz、Glòria Martrus、Fenja L.Steinert、Max Kaufmann、Adrian F.Sagebiel、Renée R.C.E.Schreurs、Anne Rechtien、Martin E.Baumdick、Johannes M.Jung、Kimberly J.M?ller、Lucy Wegner、Cordula Grüttner、Laura Richert、Roland Thünauer、Jennifer Schroeder-Schwarz、Johannes B.van Goudoever、Teunis B.H.Geijtenbeek、Marcus Altfeld、Steven T.Pals、Daniel Perez、Paul L.Klarenbeek、Christian Tomuschat、Guido Sauter、Ingo K?nigs、Udo Schumacher、Manuel A.Friese、Nathaniel Melling、Konrad Reinshagen、Madeleine J.Bunders

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作者单位：

Department of Virus Immunology,Leibniz Institute of Virology,Hamburg 20251,Germany

University Medical Center Hamburg-Eppendorf,Hamburg 20246,Germany

Institute of Neuroimmunology and Multiple Sclerosis,Center for Molecular Neurobiology Hamburg,University Medical Center Hamburg-Eppendorf,Hamburg 20251,Germany

Department of General,Visceral and Thoracic Surgery,University Medical Center Hamburg-Eppendorf,Hamburg 20246,Germany

Department of Experimental Immunology

Amsterdam Infection&Immunity Institute,Amsterdam University Medical Center,University of Amsterdam,Amsterdam 1105 AZ,The Netherlands

Department of Pediatrics,Emma Children's Hospital,Amsterdam University Medical Center,University of Amsterdam and Vrije Universiteit Amsterdam,Amsterdam 1105 AZ,The Netherlands

I.Department of Medicine,University Medical Center Hamburg-Eppendorf,Hamburg 20246,Germany

Partner Site Hamburg-Lübeck-Borstel-Riems,German Center for Infection Research(DZIF),Hamburg 20246,Germany

University of Bordeaux,Institut National de la Santé et de la Recherche Médicale,Bordeaux Population Health Research Center UMR1219 and INRIA SISTM Team,Bordeaux 33000,France

Institute of Anatomy and Experimental Morphology,University Medical Center Hamburg-Eppendorf,Hamburg 20246,Germany

Department of Pathology,Amsterdam University Medical Center,University of Amsterdam,Amsterdam 1105 AZ,The Netherlands

Department of Rheumatology and Clinical Immunology and Department of Experimental Immunology,Amsterdam Infection&Immunity Institute,Amsterdam University Medical Center,University of Amsterdam,Amsterdam 1007 MB,The Netherlands

Amsterdam Rheumatology&Immunology Center,Amsterdam University Medical Center,University of Amsterdam,Amsterdam 1105 AZ,The Netherlands

Department of Pediatric Surgery,University Medical Center Hamburg-Eppendorf,Hamburg 20246,Germany

Institute of Pathology,University Medical Center Hamburg-Eppendorf,Hamburg 20246,Germany.16Department of Pediatric Surgery,Altona Children's Hospital,Hamburg 22763,Germany

III.Department of Medicine,University Medical Center Hamburg-Eppendorf,Hamburg 20246,Germany

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基金：

Innovative Antiviral Therapy ProgramLeibniz Institute of Virology(LIV)German Center for Infection Research(DZIF)EFRE 2014-2020 REACT-EUDutch Digestive FundDeutsche ForschungsgemeinschaftHüet Ro?ll Foundationa Walter Benjamin Fellowship of the Deutsche Forschungsgemeinschafta Walter Benjamin Fellowship of the Deutsche ForschungsgemeinschaftFree and Hanseatic City of HamburgFederal Ministry of Health

项目编号：

MLDS CDG 15-02BU 3630/2-1KA5554/1-1KA5554/1-2

出版年：

2023

DOI：

10.1038/s41423-022-00944-4

中国免疫学杂志(英文版)

中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI

影响因子：0.731

ISSN：1672-7681

年,卷(期)：2023.20(2)

参考文献量61