CD25+ T Cells Induce Helicobacter Pylori-specific CD25- T-cell Anergy but Are Not Required to Maintain Persistent Hyporesponsiveness

Overview

Journal Eur J Immunol

Specialty Allergy & Immunology

Date 2008 Nov 13

PMID 19003932

Citations 8

Authors

Kathleen A Stuller

Hua Ding

Raymond W Redline

Steven J Czinn

Thomas G Blanchard

Affiliations

Soon will be listed here.

Abstract

The gastric pathogen Helicobacter pylori infects over half the world's population. The lifelong infection induces gastric inflammation but the host fails to generate protective immunity. To study the lack of protective H. pylori immunity, CD4(+)CD25(+) T(reg) cells were investigated for their ability to down-regulate H. pylori-specific CD4(+)CD25(-) cells in a murine model. CD25(-) lymphocytes from infected mice were hyporesponsive to antigenic stimulation in vitro even in the absence of CD25(+) T(reg) cells unless treated with high-dose IL-2. Transfer of CD45RB(hi) naïve CD25(-) cells from infected mice into rag1(-/-) mice challenged with H. pylori resulted in severe gastritis and reduced bacterial loads, whereas transfer of CD45RB(lo) memory CD25(-) cells from H. pylori-infected mice resulted in only mild gastritis and persistent infection. CD25(-) cells stimulated in the absence of CD25(+) cells in rag1(-/-) mice promoted bacterial clearance, but lost this ability when subsequently transferred to WT mice harboring CD25(+) cells. These results demonstrate that CD25(+) cells induce anergy in CD25(-) cells in response to H. pylori infection but are not required to maintain hyporesponsiveness. In addition, CD25(+) cells are able to suppress previously activated CD25(-) cells when responding to H. pylori challenge in vivo.

Citing Articles

The correlation of Th22 and regulatory T cells with Helicobacter pylori infection in patients with chronic gastritis.

Yao B, Xu X, Liu W, Zhang Q, Wang W, Huang Z Immun Inflamm Dis. 2023; 11(1):e768.

PMID: 36705412 PMC: 9846114. DOI: 10.1002/iid3.768.

Male-Dependent Promotion of Colitis in 129 Mice Co-Infected with and .

Ge Z, Ge L, Muthupalani S, Feng Y, Fox J Int J Mol Sci. 2020; 21(23).

PMID: 33255175 PMC: 7727654. DOI: 10.3390/ijms21238886.

Self and microbiota-derived epitopes induce CD4 T cell anergy and conversion into CD4Foxp3 regulatory cells.

Kuczma M, Szurek E, Cebula A, Ngo V, Pietrzak M, Kraj P Mucosal Immunol. 2020; 14(2):443-454.

PMID: 33139845 PMC: 7946630. DOI: 10.1038/s41385-020-00349-4.

A Case of Persistent Helicobacter pylori Infection Occurring with Anti-IgE Immunosuppression.

Zandman D, Hahn W, Moss S ACG Case Rep J. 2015; 1(1):16-8.

PMID: 26157810 PMC: 4435255. DOI: 10.14309/crj.2013.8.

Vaccinating against Helicobacter pylori in the developing world.

Zawahir S, Czinn S, Nedrud J, Blanchard T Gut Microbes. 2013; 4(6):568-76.

PMID: 24253617 PMC: 3928166. DOI: 10.4161/gmic.27093.

References

Karttunen R . Blood lymphocyte proliferation, cytokine secretion and appearance of T cells with activation surface markers in cultures with Helicobacter pylori. Comparison of the responses of subjects with and without antibodies to H. pylori. Clin Exp Immunol. 1991; 83(3):396-400. PMC: 1535340. DOI: 10.1111/j.1365-2249.1991.tb05650.x. View

Lundgren A, Suri-Payer E, Enarsson K, Svennerholm A, Lundin B . Helicobacter pylori-specific CD4+ CD25high regulatory T cells suppress memory T-cell responses to H. pylori in infected individuals. Infect Immun. 2003; 71(4):1755-62. PMC: 152046. DOI: 10.1128/IAI.71.4.1755-1762.2003. View

Blumberg R, Saubermann L, Strober W . Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. Curr Opin Immunol. 2000; 11(6):648-56. DOI: 10.1016/s0952-7915(99)00032-1. View

Anderson K, Czinn S, Redline R, Blanchard T . Induction of CTLA-4-mediated anergy contributes to persistent colonization in the murine model of gastric Helicobacter pylori infection. J Immunol. 2006; 176(9):5306-13. DOI: 10.4049/jimmunol.176.9.5306. View

Matsumoto Y, Blanchard T, Drakes M, Basu M, Redline R, Levine A . Eradication of Helicobacter pylori and resolution of gastritis in the gastric mucosa of IL-10-deficient mice. Helicobacter. 2005; 10(5):407-15. DOI: 10.1111/j.1523-5378.2005.00349.x. View

Garhart C, Redline R, Nedrud J, Czinn S . Clearance of Helicobacter pylori Infection and Resolution of Postimmunization Gastritis in a Kinetic Study of Prophylactically Immunized Mice. Infect Immun. 2002; 70(7):3529-38. PMC: 128038. DOI: 10.1128/IAI.70.7.3529-3538.2002. View

Beswick E, Pinchuk I, Das S, Powell D, Reyes V . Expression of the programmed death ligand 1, B7-H1, on gastric epithelial cells after Helicobacter pylori exposure promotes development of CD4+ CD25+ FoxP3+ regulatory T cells. Infect Immun. 2007; 75(9):4334-41. PMC: 1951191. DOI: 10.1128/IAI.00553-07. View

Fontenot J, Gavin M, Rudensky A . Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003; 4(4):330-6. DOI: 10.1038/ni904. View

Hori S, Nomura T, Sakaguchi S . Pillars Article: Control of Regulatory T Cell Development by the Transcription Factor Foxp3. Science 2003. 299: 1057-1061. J Immunol. 2017; 198(3):981-985. View

10.

Lundgren A, Stromberg E, Sjoling A, Lindholm C, Enarsson K, Edebo A . Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients. Infect Immun. 2004; 73(1):523-31. PMC: 538965. DOI: 10.1128/IAI.73.1.523-531.2005. View

11.

Seifarth C, Funk A, Reich K, Dahne I, Classen M, Deusch K . Selective increase of CD4+ and CD25+ T cells but not of gamma delta T cells in H. pylori associated gastritis. Adv Exp Med Biol. 1995; 371B:931-4. View

12.

Eaton K, Mefford M . Cure of Helicobacter pylori infection and resolution of gastritis by adoptive transfer of splenocytes in mice. Infect Immun. 2001; 69(2):1025-31. PMC: 97983. DOI: 10.1128/IAI.69.2.1025-1031.2001. View

13.

Rahn W, Redline R, Blanchard T . Molecular analysis of Helicobacter pylori-associated gastric inflammation in naïve versus previously immunized mice. Vaccine. 2004; 23(6):807-18. DOI: 10.1016/j.vaccine.2004.06.051. View

14.

Takahashi T, KUNIYASU Y, Toda M, Sakaguchi N, Itoh M, Iwata M . Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol. 1999; 10(12):1969-80. DOI: 10.1093/intimm/10.12.1969. View

15.

Lee C, Rao V, Rogers A, Ge Z, Erdman S, Whary M . 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. Infect Immun. 2007; 75(6):2699-707. PMC: 1932875. DOI: 10.1128/IAI.01788-06. View

16.

Stromberg E, Lundgren A, Edebo A, Lundin S, Svennerholm A, Lindholm C . Increased frequency of activated T-cells in the Helicobacter pylori-infected antrum and duodenum. FEMS Immunol Med Microbiol. 2003; 36(3):159-68. DOI: 10.1016/S0928-8244(03)00026-9. View

17.

Raghavan S, Fredriksson M, Svennerholm A, Holmgren J, Suri-Payer E . Absence of CD4+CD25+ regulatory T cells is associated with a loss of regulation leading to increased pathology in Helicobacter pylori-infected mice. Clin Exp Immunol. 2003; 132(3):393-400. PMC: 1808721. DOI: 10.1046/j.1365-2249.2003.02177.x. View

18.

Gottwein J, Blanchard T, Targoni O, Eisenberg J, Zagorski B, Redline R . Protective anti-Helicobacter immunity is induced with aluminum hydroxide or complete Freund's adjuvant by systemic immunization. J Infect Dis. 2001; 184(3):308-14. DOI: 10.1086/322032. View

19.

Malaty H, Graham D . Importance of childhood socioeconomic status on the current prevalence of Helicobacter pylori infection. Gut. 1994; 35(6):742-5. PMC: 1374869. DOI: 10.1136/gut.35.6.742. View

20.

Doidge C, Crust I, Lee A, Buck F, Hazell S, Manne U . Therapeutic immunisation against Helicobacter infection. Lancet. 1994; 343(8902):914-5. DOI: 10.1016/s0140-6736(94)90032-9. View