CXCR5PD-1 CD4 T Cells Colonize Infant Intestines Early in Life and Promote B Cell Maturation

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 CXCR5PD-1 CD4 T cells (T cells). We investigated the ontogeny of CXCR5PD-1 CD4 T cells in human intestines. While CXCR5PD-1 CD4 T cells were absent in fetal intestines, CXCR5PD-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 gene signature in infant intestines compared to blood. Co-cultures of autologous infant intestinal CXCR5PD-1CD4 T cells with B cells further demonstrated that infant intestinal T cells were able to effectively promote class switching and antibody production by B cells. Taken together, we demonstrate that functional T cells are numerous in infant intestines, making them a promising target for oral pediatric vaccine strategies.