title: Increased presence of effector lymphocytes during Helicobacter hepaticus-induced colitis.
abstract: OBJECTIVE
  To identify and characterize drosophila mothers against decapentaplegic (SMAD)3-dependent changes in immune cell populations following infection with Helicobacter hepaticus (H. hepaticus).
  
  
  METHODS
  SMAD3(-/-) (n = 19) and colitis-resistant SMAD3(+/-) (n = 24) mice (8-10 wk of age) were infected with H. hepaticus and changes in immune cell populations [T lymphocytes, natural killer (NK) cells, T regulatory cells] were measured in the spleen and mesenteric lymph nodes (MsLNs) at 0 d, 3 d, 7 d and 28 d post-infection using flow cytometry. Genotype-dependent changes in T lymphocytes and granzyme B(+) cells were also assessed after 28 d in proximal colon tissue using immunohistochemistry.
  
  
  RESULTS
  As previously observed, SMAD3(-/-), but not SMAD3(+/-) mice, developed colitis, peaking at 4 wk post-infection. No significant changes in T cell subsets were observed in the spleen or in the MsLNs between genotypes at any time point. However, CD4(+) and CD8(+)/CD62L(lo) cells, an effector T lymphocyte population, as well as NK cells (NKp46/DX5(+)) were significantly higher in the MsLNs of SMAD3(-/-) mice at 7 d and 28 d post-infection. In the colon, a higher number of CD3(+) cells were present in SMAD3(-/-) compared to SMAD3(+/-) mice at baseline, which did not significantly change during infection. However, the number of granzyme B(+) cells, a marker of cytolytic lymphocytes, significantly increased in SMAD3(-/-) mice 28 d post-infection compared to both SMAD3(+/-) mice and to baseline values. This was consistent with more severe colitis development in these animals.
  
  
  CONCLUSIONS
  Data suggest that defects in SMAD3 signaling increase susceptibility to H. hepaticus-induced colitis through aberrant activation and/or dysregulation of effector lymphocytes.
authors.affiliation: Department of Food Science and Human Nutrition, College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824, United States.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: McCaskey
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Rondini
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Clinthorne
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Langohr
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Gardner
authors.forename: Jenifer I
authors.initials: JI
authors.lastname: Fenton
mesh_terms: D000818:Animals; D003092:Colitis / Q000276:immunology* / Q000382:microbiology*; D003106:Colon / Q000166:cytology / Q000276:immunology / Q000473:pathology; D005260:Female; D053804:Granzymes / Q000378:metabolism; D044923:Helicobacter hepaticus / Q000276:immunology* / Q000472:pathogenicity*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology; D051900:Smad3 Protein / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D051900:Smad3 Protein; D053804:Granzymes