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Infection and Immunity, September 1999, p. 4594-4602, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Murine Splenocytes Induce Severe Gastritis and
Delayed-Type Hypersensitivity and Suppress Bacterial Colonization in
Helicobacter pylori-Infected SCID Mice
Kathryn A.
Eaton,*
Susan R.
Ringler, and
Stephen
J.
Danon
Department of Veterinary Biosciences, Ohio
State University, Columbus, Ohio 43210
Received 7 December 1998/Returned for modification 3 February
1999/Accepted 1 June 1999
The goal of this study was to evaluate the role of host immunity in
gastritis and epithelial damage due to Helicobacter pylori. Splenocytes from H. pylori-infected and uninfected C57BL/6
mice were adoptively transferred to H. pylori-infected and
uninfected severe combined immunodeficient (SCID) mice. Transfer was
verified by flow cytometry, and all mice were evaluated for the
presence of delayed-type hypersensitivity (DTH) by footpad inoculation with sterile H. pylori sonicate and for humoral immunity by
enzyme-linked immunosorbent assay. The severity of gastritis and
gastric epithelial damage was quantified histologically, epithelial
proliferation was determined by proliferating cell nuclear antigen
staining, and colonization was quantified by culture. C57BL/6 mice, but not nonrecipient SCID mice, developed moderate gastritis in response to
H. pylori. In contrast, recipient SCID mice developed
severe gastritis involving 50 to 100% of the gastric mucosa and strong DTH responses not present in C57BL/6 mice. DTH, but not serum anti-H. pylori immunoglobulin G, correlated with adoptive
transfer, gastritis, and bacterial clearance. Severe gastritis, but not bacterial colonization, was associated with epithelial metaplasia, erosions, and an elevated labeling index. This study demonstrates that
(i) adaptive immunity is essential for development of gastritis due to
H. pylori in mice, (ii) T-cell-enriched lymphocytes in SCID
mice induce DTH and gastritis, which is more severe than donor
gastritis, and (iii) the host inflammatory response, not direct
bacterial contact, causes epithelial damage. The greater severity of
gastritis in recipient SCID mice than in donor C57BL/6 mice suggests
that gastritis is due to specific T-cell subsets and/or the absence of
regulatory cell subsets in the transferred splenocytes.
*
Corresponding author. Mailing address: Department of
Veterinary Biosciences, Ohio State University, 1925 Coffey Rd.,
Columbus, OH 43210. Phone: (614) 292-9667. Fax: (614) 292-6473. E-mail: eaton.1{at}osu.edu.
Infection and Immunity, September 1999, p. 4594-4602, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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