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PMID: 12761151 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Vaccine-induced protection against Helicobacter pylori in mice lacking both antibodies and interleukin-4.

Infection and immunity ·Vol. 71 ·No. 6 ·2003-06-00 ·Pages 3628-33

Garhart CA, Nedrud JG, Heinzel FP, Sigmund NE, Czinn SJ

Abstract

To test the hypothesis that a Th2 response to Helicobacter pylori is necessary for protection and to address the possibility that humoral and Th2 cellular responses may compensate for each other, we generated mice deficient in both interleukin-4 (IL-4) and antibodies. The immunized double-knockout mice were protected from H. pylori challenge, as were the parental strains and wild-type C57BL/6 mice. Neutralization of IL-4 in B-cell-deficient mice did not prevent protection. Immunized IL-5-deficient mice were also protected. Thus, IL-4 and IL-5 are not essential for protection.

MeSH Terms
Animals Antibodies, Bacterial/physiology Bacterial Vaccines/immunology Gastritis/etiology Helicobacter pylori/immunology Immunization Interleukin-4/physiology Interleukin-5/physiology Male Mice Mice, Inbred C57BL Mice, Knockout Phenotype Th2 Cells/immunology
Chemicals
Antibodies, Bacterial Bacterial Vaccines Interleukin-5 Interleukin-4
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Garhart Christine A
Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA. [email protected]
Nedrud John G
Heinzel Frederick P
Sigmund Norma E
Czinn Steven J
References (48)
48 references, click to expand
  1. Helicobacter pylori and the pathogenesis of gastroduodenal inflammation.
    J Infect Dis. 1990 Apr;161(4):626-33 PMID: 2181029
  2. Nasal immunization induces Haemophilus influenzae-specific Th1 and Th2 responses with mucosal IgA and systemic IgG antibodies for protective immunity.
    J Infect Dis. 1999 Jul;180(1):122-32 PMID: 10353870
  3. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene.
    Nature. 1991 Apr 4;350(6317):423-6 PMID: 1901381
  4. Mucosal priming of T-lymphocyte responses to fed protein antigens using cholera toxin as an adjuvant.
    Immunology. 1991 Mar;72(3):323-8 PMID: 1709138
  5. Helicobacter pylori infection and the risk of gastric carcinoma.
    N Engl J Med. 1991 Oct 17;325(16):1127-31 PMID: 1891020
  6. Generation and analysis of interleukin-4 deficient mice.
    Science. 1991 Nov 1;254(5032):707-10 PMID: 1948049
  7. In vivo role of interleukin 4 in T cell tolerance induced by aqueous protein antigen.
    J Exp Med. 1993 Feb 1;177(2):457-63 PMID: 8426114
  8. Disruption of the murine IL-4 gene blocks Th2 cytokine responses.
    Nature. 1993 Mar 18;362(6417):245-8 PMID: 8384701
  9. Cholera toxin adjuvant greatly promotes antigen priming of T cells.
    Eur J Immunol. 1993 Sep;23(9):2136-43 PMID: 8370397
  10. Helper T cell subsets for immunoglobulin A responses: oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosa associated tissues.
    J Exp Med. 1993 Oct 1;178(4):1309-20 PMID: 8376936
  11. Impaired mucosal immune responses in interleukin 4-targeted mice.
    J Exp Med. 1995 Jan 1;181(1):41-53 PMID: 7807021
  12. Endogenous IL-12 is required for control of Th2 cytokine responses capable of exacerbating leishmaniasis in normally resistant mice.
    J Immunol. 1995 Jul 15;155(2):730-9 PMID: 7608551
  13. Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4.
    J Immunol. 1995 Nov 15;155(10):4621-9 PMID: 7594461
  14. Role of the host in pathogenesis of Helicobacter-associated gastritis: H. felis infection of inbred and congenic mouse strains.
    Infect Immun. 1996 Jan;64(1):238-45 PMID: 8557346
  15. IL-5-deficient mice have a developmental defect in CD5+ B-1 cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses.
    Immunity. 1996 Jan;4(1):15-24 PMID: 8574848
  16. Oral immunization of interleukin-4 (IL-4) knockout mice with a recombinant Salmonella strain or cholera toxin reveals that CD4+ Th2 cells producing IL-6 and IL-10 are associated with mucosal immunoglobulin A responses.
    Infect Immun. 1996 May;64(5):1516-25 PMID: 8613355
  17. Helicobacter-specific cell-mediated immune responses display a predominant Th1 phenotype and promote a delayed-type hypersensitivity response in the stomachs of mice.
    J Immunol. 1996 Jun 15;156(12):4729-38 PMID: 8648119
  18. Helicobacter pylori cagA gene and expression of cytokine messenger RNA in gastric mucosa.
    Gastroenterology. 1996 Jun;110(6):1744-52 PMID: 8964399
  19. Helicobacter pylori infection in interleukin-4-deficient and transgenic mice.
    Scand J Gastroenterol. 1999 Oct;34(10):987-92 PMID: 10563668
  20. Therapeutic immunization against Helicobacter pylori infection in the absence of antibodies.
    Immunol Cell Biol. 2000 Feb;78(1):28-30 PMID: 10651926
  21. Helicobacter pylori-induced mucosal inflammation is Th1 mediated and exacerbated in IL-4, but not IFN-gamma, gene-deficient mice.
    J Immunol. 2000 Jul 15;165(2):1022-9 PMID: 10878379
  22. Helicobacter pylori infection in wild-type and cytokine-deficient C57BL/6 and BALB/c mouse mutants.
    Microbes Infect. 2000 May;2(6):593-7 PMID: 10884609
  23. The immune response against Helicobacter pylori--a direct linkage to the development of gastroduodenal disease.
    Microbes Infect. 2000 Jul;2(9):1073-7 PMID: 10967287
  24. The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer.
    Annu Rev Microbiol. 2000;54:615-40 PMID: 11018139
  25. Immunity against Helicobacter pylori: significance of interleukin-4 receptor alpha chain status and gender of infected mice.
    Infect Immun. 2001 Jan;69(1):556-8 PMID: 11119552
  26. Adoptive transfer of CD4+ T cells specific for subunit A of Helicobacter pylori urease reduces H. pylori stomach colonization in mice in the absence of interleukin-4 (IL-4)/IL-13 receptor signaling.
    Infect Immun. 2001 Mar;69(3):1714-21 PMID: 11179348
  27. The design of vaccines against Helicobacter pylori and their development.
    Annu Rev Immunol. 2001;19:523-63 PMID: 11244046
  28. Protective anti-Helicobacter immunity is induced with aluminum hydroxide or complete Freund's adjuvant by systemic immunization.
    J Infect Dis. 2001 Aug 1;184(3):308-14 PMID: 11443556
  29. Clearance of Helicobacter pylori Infection and Resolution of Postimmunization Gastritis in a Kinetic Study of Prophylactically Immunized Mice.
    Infect Immun. 2002 Jul;70(7):3529-38 PMID: 12065492
  30. Protection against Helicobacter pylori infection following immunization is IL-12-dependent and mediated by Th1 cells.
    J Immunol. 2002 Dec 15;169(12):6977-84 PMID: 12471132
  31. Vaccine-induced reduction of Helicobacter pylori colonization in mice is interleukin-12 dependent but gamma interferon and inducible nitric oxide synthase independent.
    Infect Immun. 2003 Feb;71(2):910-21 PMID: 12540573
  32. Unidentified curved bacilli on gastric epithelium in active chronic gastritis.
    Lancet. 1983 Jun 4;1(8336):1273-5 PMID: 6134060
  33. Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets.
    J Exp Med. 1989 Jan 1;169(1):59-72 PMID: 2521244
  34. T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum of patients with peptic ulcer disease.
    J Immunol. 1997 Jan 15;158(2):962-7 PMID: 8993017
  35. Atrophic gastric changes in both Helicobacter felis and Helicobacter pylori infected mice are host dependent and separate from antral gastritis.
    Gut. 1996 Nov;39(5):639-48 PMID: 9026476
  36. A standardized mouse model of Helicobacter pylori infection: introducing the Sydney strain.
    Gastroenterology. 1997 Apr;112(4):1386-97 PMID: 9098027
  37. Catalase, a novel antigen for Helicobacter pylori vaccination.
    Infect Immun. 1997 Nov;65(11):4668-74 PMID: 9353048
  38. Murine CD4 T-cell response to Helicobacter infection: TH1 cells enhance gastritis and TH2 cells reduce bacterial load.
    Gastroenterology. 1997 Dec;113(6):1848-57 PMID: 9394724
  39. Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype.
    Gastroenterology. 1998 Mar;114(3):482-92 PMID: 9496938
  40. Rectal and intranasal immunizations with recombinant urease induce distinct local and serum immune responses in mice and protect against Helicobacter pylori infection.
    Infect Immun. 1998 Jun;66(6):2879-86 PMID: 9596763
  41. Systemic immunization with urease protects mice against Helicobacter pylori infection.
    Vaccine. 1998 May;16(8):850-6 PMID: 9627943
  42. Immunization of BALB/c mice with Helicobacter urease B induces a T helper 2 response absent in Helicobacter infection.
    Gastroenterology. 1998 Oct;115(4):891-7 PMID: 9753492
  43. Local cytokine response in Helicobacter pylori-infected subjects.
    Infect Immun. 1998 Dec;66(12):5964-71 PMID: 9826379
  44. Immunization of mice with urease vaccine affords protection against Helicobacter pylori infection in the absence of antibodies and is mediated by MHC class II-restricted responses.
    J Exp Med. 1998 Dec 21;188(12):2277-88 PMID: 9858514
  45. Antibody-independent protective mucosal immunity to gastric helicobacter infection in mice.
    Cell Immunol. 1999 Jan 10;191(1):74-80 PMID: 9918689
  46. IL-4 and IL-10 are both required for the induction of oral tolerance.
    J Immunol. 1999 Mar 1;162(5):2613-22 PMID: 10072503
  47. Comparison between targeted and untargeted systemic immunizations with adjuvanted urease to cure Helicobacter pylori infection in mice.
    Vaccine. 1999 Mar 5;17(9-10):1130-5 PMID: 10195624
  48. Monoclonal antibodies block murine IL-4 receptor function.
    J Immunol. 1990 Jun 1;144(11):4212-7 PMID: 1692858
Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.71.6.3628-3633.2003
Email
[email protected]
Published
2003-06-00
Pages
3628-33
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC155749
Subset
IM
Grants
NIAID NIH HHS · P01 AI036359 · United States
NIAID NIH HHS · AI-45602 · United States
NCI NIH HHS · CA-73515 · United States
NIAID NIH HHS · AI-35979 · United States
NIAID NIH HHS · R01 AI045602 · United States
NIDDK NIH HHS · R01 DK046461 · United States
NIDDK NIH HHS · R56 DK046461 · United States
NIAID NIH HHS · AI-36359 · United States
NIDDK NIH HHS · DK-46461 · United States
NIAID NIH HHS · AI-40701 · United States
NCI NIH HHS · T32 CA073515 · United States
External Links
PubMed source DOI: 10.1128/IAI.71.6.3628-3633.2003 PMC Full Text View journal details
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