Effects of microflora on the neonatal development of gut mucosal T cells and myeloid cells in the mouse

Abstract

Summary Colonization with commensal flora in very early life may profoundly influence intestinal lymphoid development and bias later immune responses. We defined gut‐homing T cell phenotypes and the influence of flora on intestinal immune development in mice. Intestinal T cells were phenotyped and quantified in conventional (CV), germfree (GF) and conventionalized germfree (GF/CV) neonatal mice by immunohistochemistry. Mucosal adressin cell adhesion molecule 1 (MAdCAM‐1) was expressed by mucosal vessels at birth in CV and GF mice and was more prevalent in CV than GF small intestine, but was distributed similarly and did not change with age. Less MAdCAM‐1 was expressed in the colon; its distribution became restricted after weaning, with no difference between CV and GF mice. CD3+β7+ cells were present in similar numbers in CV and GF intestine at birth. They were CD62L– in CV mice and were accompanied by further CD3+β7+CD62L– T cells as development progressed, but in GF and GF/CV intestine they expressed CD62L and numbers did not change. IEL numbers increased at weaning in CV mice in both small and large intestine, but showed delayed development in GF intestine. Macrophages were present at high levels from birth in GF intestine, but dendritic cells did not develop until day 16. Thus, fetus‐derived T cells seed the intestinal lamina propria before birth via β–MadCAM interactions. Their activation status depends on the microbiological status of the dam, and without a commensal flora they remain naive. We propose that these cells regulate antigen responsiveness of the developing mucosal T cell pool.

Intestinal macrophages – specialised adaptation to a unique environment

“…These populations have been shown to derive from a myeloid precursor during embryonic development, which is then maintained through self-renewal in the tissue [50]. Although intestinal Mjs are claimed not to proliferate under steadystate conditions [10], adoptively transferred monocytes can undergo marked clonal expansion in the mucosa of MPdepleted recipients [9] and Mjs clearly populate the intestine before birth [40,51]. The mechanisms underpinning intestinal Mj replenishment need not be mutually exclusive.…”

The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases

“…39,45 The effect of microbial colonization on innate immune cells has been documented in our studies on the development of phagocytes, dendritic cells and intestinal epithelial cells. 24,46 Interestingly, the Tcell receptor repertoire is also influenced by colonization with microorganisms. 47 Recently we have studied the effect of the microbiota on the development of lymphatic subpopulations in BALB/c mice bred in Gut microbiota and mucosal barrier diseases H Tlaskalová -Hogenová et al 112 germ-free isolators or under conventional conditions and fed with sterile diets differing in contamination with microbial components.…”

Visceral Pain and Gastrointestinal Microbiome

“…[15][16][17] Similarly, in humans, alterations in the pattern of GI colonization are thought to have long-term consequences on immune function.…”