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

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.Möller Lucy Wegner Cordula Grüttner Laura Richert Roland Thünauer Jennifer Schroeder-Schwarz Johannes Bvan Goudoever Teunis B.H.Geijtenbeek Marcus Altfeld Steven T.Pals Daniel Perez Paul L.Klarenbeek Christian Tomuschat Guido Sauter Ingo Königs Udo Schumacher Manuel A.Friese Nathaniel Melling Konrad Reinshagen Madeleine J.Bunders 

机构地区：[1]Department of Virus Immunology,Leibniz Institute of Virology,Hamburg,20251,Germany [2]University Medical Center Hamburg-Eppendorf,Hamburg,20246,Germany [3]Institute of Neuroimmunology and Multiple Sclerosis,Center for Molecular Neurobiology Hamburg,University Medical Center Hamburg-Eppendorf,Hamburg,20251,Germany [4]Department of General,Visceral and Thoracic Surgery,University Medical Center Hamburg-Eppendorf,Hamburg,20246,Germany [5]Department of Experimental Immunology,Amsterdam Infection&Immunity Institute,Amsterdam University Medical Center,University of Amsterdam,Amsterdam,1105 AZ,The Netherlands [6]Department of Pediatrics,Emma Children’s Hospital,Amsterdam University Medical Center,University of Amsterdam and Vrije Universiteit Amsterdam,Amsterdam,1105 AZ,The Netherlands [7]I.Department of Medicine,University Medical Center Hamburg-Eppendorf,Hamburg,20246,Germany [8]Partner Site Hamburg-Lübeck-Borstel-Riems,German Center for Infection Research(DZIF),Hamburg,20246,Germany [9]University of Bordeaux,Institut National de la Santéet de la Recherche Médicale,Bordeaux Population Health Research Center UMR1219 and INRIA SISTM Team,Bordeaux,33000,France [10]Institute of Anatomy and Experimental Morphology,University Medical Center Hamburg-Eppendorf,Hamburg,20246,Germany [11]Department of Pathology,Amsterdam University Medical Center,University of Amsterdam,Amsterdam,1105 AZ,The Netherlands [12]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 [13]Amsterdam Rheumatology&Immunology Center,Amsterdam University Medical Center,University of Amsterdam,Amsterdam,1105 AZ,The Netherlands [14]Department of Pediatric Surgery,University Medical Center Hamburg-Eppendorf,Hamburg,20246,Germany [15]Institute of Pathology,University Medical Center Hamburg-Eppendorf,Hamburg,20246,Germany [16]Department of Pediatric Surgery,Altona Children’s Hospital

出　　处：《Cellular & Molecular Immunology》2023年第2期201-213,共13页中国免疫学杂志（英文版）

基　　金：supported by the Innovative Antiviral Therapy Program,Leibniz Institute of Virology(LIV),the German Center for Infection Research(DZIF),EFRE 2014-2020 REACT-EU,Dutch Digestive Fund(MLDS CDG 15-02);Deutsche Forschungsgemeinschaft(BU 3630/2-1);Hüet Roëll Foundation.MK is supported by a Walter Benjamin Fellowship of the Deutsche Forschungsgemeinschaft(KA5554/1-1,KA5554/1-2);The Leibniz Institute of Virology is supported by the Free and Hanseatic City of Hamburg and the Federal Ministry of Health.

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.

关 键 词：TFH cells B cells Antibodies INTESTINE PEDIATRICS 

分 类 号：R285.5[医药卫生—中药学]