Jordan-Paiz A, Martrus G, Steinert FL, Kaufmann M, Sagebiel AF, Schreurs RRCE, Rechtien A, Baumdick ME, Jung JM, Möller KJ, Wegner L, Grüttner C, Richtert L, Thünauer R, Schroeder-Schwarz J, von Goudoever JB, Geijtenbeek TBH, Altfeld M, Pals ST, Perez D, Klarenbeek PL, Tomuschat C, Sauter G, Königs I, Schumacher U, Friese MA, Melling N, Reinshagen K, Bunders MJ.

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. 



Cell Mol Immunol. 2023 Jan 5.



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