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

Ana Jordan-PaizGlòria MartrusFenja L SteinertMax KaufmannAdrian F SagebielRenée R C E SchreursAnne RechtienMartin E BaumdickJohannes M JungKimberly J MöllerLucy WegnerCordula GrüttnerLaura RichertRoland ThünauerJennifer Schroeder-SchwarzJohannes B van GoudoeverTeunis B H GeijtenbeekMarcus AltfeldSteven T PalsDaniel PerezPaul L KlarenbeekChristian TomuschatGuido SauterIngo KönigsUdo SchumacherManuel A FrieseNathaniel MellingKonrad ReinshagenMadeleine J Bunders
Published in: Cellular & molecular immunology (2023)
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 (T FH 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 T FH 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 T FH cells were able to effectively promote class switching and antibody production by B cells. Taken together, we demonstrate that functional T FH cells are numerous in infant intestines, making them a promising target for oral pediatric vaccine strategies.
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