학술논문
CXCR5+ PD-1++ CD4+ T cells colonize infant intestines early in life and promote B cell maturation
Document Type
Original Paper
Author
Jordan-Paiz, Ana; Martrus, Glòria; Steinert, Fenja L.; Kaufmann, Max; Sagebiel, Adrian F.; Schreurs, Renée R. C. E.; Rechtien, Anne; Baumdick, Martin E.; Jung, Johannes M.; Möller, Kimberly J.; Wegner, Lucy; Grüttner, Cordula; Richert, Laura; Thünauer, Roland; Schroeder-Schwarz, Jennifer; van Goudoever, Johannes B.; Geijtenbeek, Teunis B. H.; Altfeld, Marcus; Pals, Steven T.; Perez, Daniel; Klarenbeek, Paul L.; Tomuschat, Christian; Sauter, Guido; Königs, Ingo; Schumacher, Udo; Friese, Manuel A.; Melling, Nathaniel; Reinshagen, Konrad; Bunders, Madeleine J.
Source
Cellular & Molecular Immunology. 20(2):201-213
Subject
Language
English
ISSN
2042-0226
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.