@article{ba08fc7461d44a10a391f733123583f7,
title = "CXCR5+PD-1++ CD4+ T cells colonize infant intestines early in life and promote B cell maturation",
abstract = "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.",
keywords = "Antibodies, B cells, Intestine, Pediatrics, TFH cells",
author = "Ana Jordan-Paiz and Gl{\`o}ria Martrus and Steinert, \{Fenja L.\} and Max Kaufmann and Sagebiel, \{Adrian F.\} and Schreurs, \{Ren{\'e}e R. C. E.\} and Anne Rechtien and Baumdick, \{Martin E.\} and Jung, \{Johannes M.\} and M{\"o}ller, \{Kimberly J.\} and Lucy Wegner and Cordula Gr{\"u}ttner and Laura Richert and Roland Th{\"u}nauer and Jennifer Schroeder-Schwarz and \{van Goudoever\}, \{Johannes B.\} and Geijtenbeek, \{Teunis B. H.\} and Marcus Altfeld and Pals, \{Steven T.\} and Daniel Perez and Klarenbeek, \{Paul L.\} and Christian Tomuschat and Guido Sauter and Ingo K{\"o}nigs and Udo Schumacher and Friese, \{Manuel A.\} and Nathaniel Melling and Konrad Reinshagen and Bunders, \{Madeleine J.\}",
note = "Funding Information: The authors would like to thank all donors for participating in this study; Dr. Weijer, Mrs. Voordouw, Mrs. Siteur-van Rijnstra, and the Bloemenhove Clinic (Heemstede, the Netherlands) for collecting and providing fetal tissues. The authors also thank the FACS Core facility members of the Leibniz Institute of Virology (LIV) for their support, Mr. Arne D{\"u}sedau and Mrs. Jana Henessen. This study is 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) and H{\"u}et Ro{\"e}ll 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. Funding Information: The authors would like to thank all donors for participating in this study; Dr. Weijer, Mrs. Voordouw, Mrs. Siteur-van Rijnstra, and the Bloemenhove Clinic (Heemstede, the Netherlands) for collecting and providing fetal tissues. The authors also thank the FACS Core facility members of the Leibniz Institute of Virology (LIV) for their support, Mr. Arne D{\"u}sedau and Mrs. Jana Henessen. This study is 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) and H{\"u}et Ro{\"e}ll 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. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to CSI and USTC.",
year = "2023",
month = feb,
doi = "10.1038/s41423-022-00944-4",
language = "English",
volume = "20",
pages = "201--213",
journal = "Cellular \& molecular immunology",
issn = "1672-7681",
publisher = "Nature Publishing Group",
number = "2",
}