Intestinal immune system

Where are memory T cells found before birth?

Memory T cells are found in various fetal tissues, including the intestines of humans and nonhuman primates (1, 2, 3, 4, 5), umbilical cord blood (6), and the placenta (7).

Does the imprinting of the adaptive intestinal immune system begin before birth?

Accordingly, the development of the gut’s adaptive immune system may already begin in utero. This suggests that the critical period for establishing intestinal homeostasis may begin before birth (8).
Despite these findings, few studies have investigated the antigens present in the womb or the metabolites that influence intestinal homeostasis during this early stage (9, 10).

Where are immune cells and T cells located in the human gut?

Approximately 70% of the body’s immune cells are located in the gut (11). The human gut is an important reservoir of T cells. These immune cells are distributed throughout the intestinal epithelium, the lamina propria, and the gut-associated lymphoid tissues (GALT), including Peyer’s patches, mesenteric lymph nodes, and isolated lymphoid follicles (12, 13, 14, 15, 16).

What roles do T cells and GALT play in the intestinal barrier and immune system?

Intraepithelial lymphocytes (IELs), primarily CD8⁺ T cells, are essential for maintaining the integrity of the intestinal barrier, immune surveillance, and defense against pathogens. CD4⁺ T cells are more commonly found in the lamina propria. GALT are essential for adaptive immune responses and contribute to the generation of effector T cells. The interaction between intestinal T cells and the gut microbiota is crucial for maintaining immune system homeostasis (12, 13, 14, 15, 16).

How does microbial colonization of the fetus influence immune system development?

During the early stages of pregnancy, the human fetal immune system begins to develop. Using 16S rRNA gene sequencing, we created a detailed profile of the microorganisms present in various fetal organs. Our research showed that during the second trimester, a low but consistent microbial presence exists in the fetal gut, skin, placenta, and lungs.
Notably, we identified several viable bacterial strains, including Staphylococcus and Lactobacillus, in fetal tissue. These bacterial strains were observed to trigger the activation of memory T cells in fetal mesenteric lymph nodes in vitro. This finding supports the hypothesis that exposure to microorganisms contributes to the immunological imprinting of the fetus (5).

How does postnatal gut colonization influence the development of lymphoid structures?

In both mice and humans, secondary lymphoid structures—such as Peyer’s patches and mesenteric lymph nodes (MLNs)—form before birth. However, their size and the development of germinal centers depend on the gut’s postnatal microbial colonization (21, 22, 23).

Which cell types accompany intestinal epithelial cells in the gut?

Intestinal epithelial cells are accompanied by enteroendocrine cells, Paneth cells, and goblet cells (17).

Which immune cells are located among the intestinal epithelial cells?

TCRαβ⁺ intraepithelial lymphocytes (IELs), TCRγδ⁺ IELs, as well as NK cells and NKT cells, are also found among the intestinal epithelial cells (17).

How do Paneth cells and goblet cells protect the intestinal barrier from pathogens?

When a pathogen enters the body, Paneth cells play a crucial role by releasing specific antibacterial molecules, such as defensins, into the intestinal villi located in the lumen of the small intestine. At the same time, goblet cells contribute by secreting mucus onto the intestinal surface, which is essential for maintaining the integrity of the intestinal barrier (18, 19).

Which innate immune cells colonize the intestinal mucosa after birth?

Innate immune cells - including lymphoid tissue inducer (LTi) cells, natural killer (NK) cells, NK-like NKp46⁺ cells, and T helper 2 - like cells - migrate from the fetal liver into the intestinal mucosa of mice during the first four weeks after birth, guided by endogenous signals (20).

References

(1) Stras et al. 2019 Dev Cell 51(3): 357-73
(2) Halkias et al. 2019 J Clin Invest 129(9): 3562-77
(3) Schreurs et al. 2019 Immunity 50(2): 462-76
(4) Li et al. 2019 Nat Immunol 20: 301-12
(5) Mishra et al. 2021
(6) Frascoli et al. 2018 Sci Transl Med 10(438): eaan2263
(7) Toothaker et al. 2020 Front Immunol 11: 866
(8) Koren et al. 2024 Nat Rev Gastroenterol Hepatol 21(1): 35-45
(9) Vuong et al. 2020
(10) Husso et al. 2023 BMC Biol 21(1): 207
(11) Yin et al. 2021a J Cell Mol Med. 25: 1332-1341
(12) Maloy & Powrie 2011 Nature 474: 298-306
(13) Ma et al. 2021 J Leukoc Biol 109: 339-347
(14) Wang et al. 2023 Int Immunopharmacol 124: 110842
(15) Wang et al. 2023l J Exp Med 220: e20221437
(16) Lockhart et al. 2024 Annu Rev Immunol 42: 289-316
(17) Zhang et al. 2019l
(18) Johansson et al. 2008 Proc. Natl. Acad. Sci. USA 105: 15064-15069
(19) Bevins & Salzman 2011 Nature Reviews Microbiology 9(5): 356-368
(20) Sawa et al. 2010 Science 330: 665-669
(21) Xiong & Raulet 2007 Immunol. Rev. 215: 15-31
(22) Weitkamp et al. 2009 Pediatr. Dev. Pathol. 12: 443-449
(23) van de Pavert & Mebius 2010 Nature Rev. Immunol. 10: 664-674

see also:
Antimicrobial Peptides (AMPs) & Paneth Cells
Development of Gut Microbiota & Prenatal development / Prenatal Life
Immune Cells / Leucocytes / White Blood Cells & Intestine / Gastrointestinal Tract (Gut / GIT)
Intestinal homeostasis
Lamina propria
Maternal microbiota