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Infection and Immunity, June 2006, p. 3519-3529, Vol. 74, No. 6
0019-9567/06/$08.00+0 doi:10.1128/IAI.01314-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Karen L. Laurie,2,
Odilia Wijburg,1,3
John Pedersen,4
Martin Pearse,5
Ian R. van Driel,2,
Paul A. Gleeson,2,
* and
Richard A. Strugnell1,3,
Department of Microbiology and Immunology and the NHMRC Bacterial Pathogenesis Group, The University of Melbourne, Parkville, Victoria 3010, Australia,1 Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia,2 CRC for Vaccine Technology, Brisbane, Australia,3 Department of Anatomical Pathology, Alfred Hospital, Prahran, Victoria 3181, Australia,4 CSL Ltd., Poplar Rd., Parkville, Victoria 3052, Australia5
Received 12 August 2005/ Returned for modification 17 November 2005/ Accepted 6 March 2006
Gastric Helicobacter spp. induce chronic gastritis that may lead to ulceration and dysplasia. The host elicits a T helper 1 (Th1) response that is fundamental to the pathogenesis of these bacteria. We analyzed immune responses in Helicobacter-infected, normal mice depleted of CD4+ CD25+ T cells to investigate the in vivo role of regulatory T cells (Tregs) in the modulation of Helicobacter immunopathology. BALB/c and transgenic mice were depleted of CD4+ CD25+ T cells by administration of an anti-CD25 antibody either at the time of infection with Helicobacter or during chronic infection and gastritis. Depletion of CD25+ Tregs prior to and during infection of mice with Helicobacter spp. did not affect either bacterial colonization or severity of gastritis. Depletion of CD25+ Tregs was associated with increased Helicobacter-specific antibody levels and an altered isotype distribution. Paragastric lymph node cells from CD25+ Treg-depleted and control infected mice showed similar proliferation to Helicobacter antigens, but only cells from anti-CD25-treated animals secreted Th2 cytokines. CD25+ Tregs do not control the level of gastritis induced by gastric Helicobacter spp. in normal, thymus-intact BALB/c mice. However, CD25+ Tregs influence the cytokine and antibody responses induced by infection. Autoimmune gastritis is not induced in Helicobacter-infected mice depleted of CD25+ Tregs but is induced in CD25+ Treg-depleted mice, which have a higher frequency of autoreactive T cells.
M.K. and K.L.L. contributed equally to this work as first authors.
I.R.V.D., P.A.G., and R.A.S. contributed equally to this work as senior authors.
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