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 (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.

Keywords: Antibodies; B cells; Intestine; Pediatrics; TFH cells.