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PMID: 17353283 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Wild-type and interleukin-10-deficient regulatory T cells reduce effector T-cell-mediated gastroduodenitis in Rag2-/- mice, but only wild-type regulatory T cells suppress Helicobacter pylori gastritis.

Infection and immunity ·Vol. 75 ·No. 6 ·2007-06-00 ·Pages 2699-707

Lee CW, Rao VP, Rogers AB, Ge Z, Erdman SE, Whary MT, Fox JG

Abstract

CD4(+) CD45RB(hi) CD25(-) effector T cells (T(E)) promote Helicobacter pylori gastritis in mice, and CD4(+) CD45RB(lo) CD25(+) regulatory T cells (T(R)) are anti-inflammatory. Using adoptive transfer into H. pylori-infected Rag2(-/-) mice, we evaluated effects of wild-type (wt) C57BL/6 or congenic interleukin-10-deficient (IL-10(-/-)) T(R) cells on gastritis, gastric cytokines, and H. pylori colonization. Infected Rag2(-/-) mice colonized in the corpus and antrum with 10(5) to 10(6) H. pylori CFU/gram without associated gastritis. T(E) cell transfer caused morbidity and an H. pylori-independent pangastritis and duodenitis (gastroduodenitis) associated with increased expression of gamma interferon (IFN-gamma) and tumor necrosis factor alpha. T(E) cell transfer to H. pylori-infected mice led to additive corpus gastritis associated with inflammatory cytokine expression and reduced colonization. wt T(R) cells reduced morbidity, H. pylori corpus gastritis, gastroduodenitis, and inflammatory cytokine expression and reversed the decline in H. pylori colonization attributable to T(E) cells. Although less effective than wt T(R) cells, IL-10(-/-) T(R) cells also reduced morbidity and gastroduodenitis but did not reduce H. pylori corpus gastritis or impact T(E) cell inhibition of colonization. Gastric tissues from mice receiving wt T(R) cells expressed higher levels of Foxp3 compared to recipients of IL-10(-/-) T(R) cells, consistent with lower regulatory activity of IL-10(-/-) T(R) cells. These results demonstrate that wt T(R) cells suppressed T(E)-cell-mediated H. pylori-independent gastroduodenitis and H. pylori-dependent corpus gastritis more effectively than IL-10(-/-) T(R) cells. Compartmental differences in T(E)-cell- and H. pylori-mediated inflammation and in regulatory effects between wt T(R) and IL-10(-/-) T(R) cells suggest that IL-10 expression by wt T(R) cells is important to regulatory suppression of gastric inflammation.

MeSH Terms
Animals DNA-Binding Proteins/deficiency Gastric Mucosa/immunology,metabolism,microbiology,pathology Gastritis/genetics,immunology,pathology Helicobacter Infections/immunology Helicobacter pylori Interleukin-10/biosynthesis,deficiency,genetics Mice Mice, Inbred C57BL Mice, Knockout T-Lymphocytes/immunology,metabolism T-Lymphocytes, Regulatory/immunology
Chemicals
DNA-Binding Proteins Rag2 protein, mouse Interleukin-10
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lee Chung-Wei
Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Rao Varada P
Rogers Arlin B
Ge Zhongming
Erdman Susan E
Whary Mark T
Fox James G
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.01788-06
Published
2007-06-00
Epub
2007-00-12
Pages
2699-707
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC1932875
Subset
IM
Grants
NIAID NIH HHS · R01 AI 37750 · United States
NIAID NIH HHS · R01 AI037750 · United States
NCI NIH HHS · P01 CA 26T31 · United States
NIEHS NIH HHS · P30 ES002109 · United States
NIAID NIH HHS · R01 AI050952 · United States
NIEHS NIH HHS · P30 ES 02109 · United States
NIAID NIH HHS · R01 AI 50952 · United States
External Links
PubMed source DOI: 10.1128/IAI.01788-06 PMC Full Text View journal details
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