title: Effects of microflora on the neonatal development of gut mucosal T cells and myeloid cells in the mouse.
abstract: 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(+)beta(7) (+) 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(+)beta(7) (+)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 beta-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.
authors.affiliation: Department of Clinical Science at South Bristol, University of Bristol, Bristol, UK.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Williams
authors.forename: Christopher S J
authors.initials: CS
authors.lastname: Probert
authors.forename: Renata
authors.initials: R
authors.lastname: Stepankova
authors.forename: Helena
authors.initials: H
authors.lastname: Tlaskalova-Hogenova
authors.forename: Anne
authors.initials: A
authors.lastname: Phillips
authors.forename: Paul W
authors.initials: PW
authors.lastname: Bland
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D016175:B-Lymphocyte Subsets / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005856:Germ-Free Life; D018928:Immunity, Mucosal; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000254:growth & development / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009088:Mucoproteins; D022423:Myeloid Cells / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D015815:Cell Adhesion Molecules; C489082:Madcam1 protein, mouse; D009088:Mucoproteins