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

Cell Mol Immunol. 2023 Feb;20(2):201-213. doi: 10.1038/s41423-022-00944-4. Epub 2023 Jan 5.


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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes
  • CD4-Positive T-Lymphocytes* / immunology
  • Child
  • Humans
  • Infant
  • Programmed Cell Death 1 Receptor*
  • Receptors, CXCR5
  • T-Lymphocytes, Helper-Inducer*


  • CXCR5 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, CXCR5