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

• Published in: Cellular & molecular immunology Vol. 20; no. 2; pp. 201 - 213
• Main Authors: Jordan-Paiz, Ana, Martrus, Glòria, Steinert, Fenja L., Kaufmann, Max, Sagebiel, Adrian F., Schreurs, Renée R. C. E., Rechtien, Anne, Baumdick, Martin E., Jung, Johannes M., Möller, Kimberly J., Wegner, Lucy, Grüttner, Cordula, Richert, Laura, Thünauer, Roland, Schroeder-Schwarz, Jennifer, van Goudoever, Johannes B., Geijtenbeek, Teunis B. H., Altfeld, Marcus, Pals, Steven T., Perez, Daniel, Klarenbeek, Paul L., Tomuschat, Christian, Sauter, Guido, Königs, Ingo, Schumacher, Udo, Friese, Manuel A., Melling, Nathaniel, Reinshagen, Konrad, Bunders, Madeleine J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-02-2023; Nature Publishing Group
• Subjects: 631/250/2504/2506; 631/250/347; Adult; Antibodies; B-Lymphocytes; Biomedical and Life Sciences; Biomedicine; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Child; Class switching; CXCR5 protein; Fetuses; Humans; Immunology; Infant; Infants; Intestine; Lymphocytes; Lymphocytes B; Lymphocytes T; Medical Microbiology; Microbiology; Ontogeny; PD-1 protein; Pediatrics; Programmed Cell Death 1 Receptor; Receptors, CXCR5; T-Lymphocytes, Helper-Inducer; Vaccine; Antibodies; Pediatrics; TFH cells; B cells; Intestine
• ISSN: 2042-0226; 1672-7681; 2042-0226
• DOI: 10.1038/s41423-022-00944-4

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.