Skip to main content
PMC home page
Clinical and Diagnostic Laboratory Immunology logoLink to Clinical and Diagnostic Laboratory Immunology
. 1997 Jul;4(4):440–446. doi: 10.1128/cdli.4.4.440-446.1997

T-cell, antibody, and cytokine responses to homologs of the 60-kilodalton heat shock protein in Helicobacter pylori infection.

S A Sharma 1, G G Miller 1, R A Peek Jr 1, G Pérez-Pérez 1, M J Blaser 1
PMCID: PMC170547  PMID: 9220161

Abstract

For Helicobacter pylori, the hsp60 heat shock protein encoded by hspB is being considered as a potential candidate for subunit vaccines. We investigated the humoral and cellular responses to H. pylori hsp60 and its cross-reactivity with the homologous Mycobacterium bovis p65 protein and autologous human hsp60 protein. H. pylori-infected persons had significantly higher levels than uninfected persons of serum immunoglobulin G antibodies recognizing H. pylori hsp60, but not M. bovis p65 or human hsp60, as determined by enzyme-linked immunosorbent assay. In contrast, immunoblotting demonstrated cross-reactivity of H. pylori hsp60 with human hsp60. T-cell recognition of H. pylori hsp60 was found in both infected and uninfected subjects, and there was no recognition of human hsp60. T cells from infected and uninfected subjects that had been activated in response to H. pylori hsp60 or M. bovis p65 were phenotypically similar but appeared to secrete different levels of gamma interferon and interleukin-10. These results demonstrate an apparent difference in the epitopes recognized by the T and B cells responding to H. pylori hsp60 in H. pylori-infected persons. In contrast to the T-cell responses, which were highly variable in all subjects and showed no recognition of autologous proteins, a specific B-cell response that may have cross-reactivity to human hsp60 is evident in some infected subjects.

Full Text

The Full Text of this article is available as a PDF (836.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barrios C., Tougne C., Polla B. S., Lambert P. H., Del Giudice G. Specificity of antibodies induced after immunization of mice with the mycobacterial heat shock protein of 65 kD. Clin Exp Immunol. 1994 Nov;98(2):224–228. doi: 10.1111/j.1365-2249.1994.tb06129.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blander S. J., Horwitz M. A. Major cytoplasmic membrane protein of Legionella pneumophila, a genus common antigen and member of the hsp 60 family of heat shock proteins, induces protective immunity in a guinea pig model of Legionnaires' disease. J Clin Invest. 1993 Feb;91(2):717–723. doi: 10.1172/JCI116253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blaser M. J. Helicobacter pylori and the pathogenesis of gastroduodenal inflammation. J Infect Dis. 1990 Apr;161(4):626–633. doi: 10.1093/infdis/161.4.626. [DOI] [PubMed] [Google Scholar]
  4. Blaser M. J. Hypotheses on the pathogenesis and natural history of Helicobacter pylori-induced inflammation. Gastroenterology. 1992 Feb;102(2):720–727. doi: 10.1016/0016-5085(92)90126-j. [DOI] [PubMed] [Google Scholar]
  5. Blaser M. J., Parsonnet J. Parasitism by the "slow" bacterium Helicobacter pylori leads to altered gastric homeostasis and neoplasia. J Clin Invest. 1994 Jul;94(1):4–8. doi: 10.1172/JCI117336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Crabtree J. E., Shallcross T. M., Heatley R. V., Wyatt J. I. Mucosal tumour necrosis factor alpha and interleukin-6 in patients with Helicobacter pylori associated gastritis. Gut. 1991 Dec;32(12):1473–1477. doi: 10.1136/gut.32.12.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Del Giudice G., Gervaix A., Costantino P., Wyler C. A., Tougne C., de Graeff-Meeder E. R., van Embden J., van der Zee R., Nencioni L., Rappuoli R. Priming to heat shock proteins in infants vaccinated against pertussis. J Immunol. 1993 Mar 1;150(5):2025–2032. [PubMed] [Google Scholar]
  8. Di Tommaso A., Xiang Z., Bugnoli M., Pileri P., Figura N., Bayeli P. F., Rappuoli R., Abrignani S., De Magistris M. T. Helicobacter pylori-specific CD4+ T-cell clones from peripheral blood and gastric biopsies. Infect Immun. 1995 Mar;63(3):1102–1106. doi: 10.1128/iai.63.3.1102-1106.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dooley C. P., Cohen H., Fitzgibbons P. L., Bauer M., Appleman M. D., Perez-Perez G. I., Blaser M. J. Prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic persons. N Engl J Med. 1989 Dec 7;321(23):1562–1566. doi: 10.1056/NEJM198912073212302. [DOI] [PubMed] [Google Scholar]
  10. Drumm B., Perez-Perez G. I., Blaser M. J., Sherman P. M. Intrafamilial clustering of Helicobacter pylori infection. N Engl J Med. 1990 Feb 8;322(6):359–363. doi: 10.1056/NEJM199002083220603. [DOI] [PubMed] [Google Scholar]
  11. Dunn B. E., Roop R. M., 2nd, Sung C. C., Sharma S. A., Perez-Perez G. I., Blaser M. J. Identification and purification of a cpn60 heat shock protein homolog from Helicobacter pylori. Infect Immun. 1992 May;60(5):1946–1951. doi: 10.1128/iai.60.5.1946-1951.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Elson C. J., Thompson S. J. Immunity, autoimmunity and immunotherapy: new frontiers in heat shock protein research. Clin Exp Immunol. 1994 Nov;98(2):175–177. doi: 10.1111/j.1365-2249.1994.tb06121.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Engstrand L., Scheynius A., Påhlson C. An increased number of gamma/delta T-cells and gastric epithelial cell expression of the groEL stress-protein homologue in Helicobacter pylori-associated chronic gastritis of the antrum. Am J Gastroenterol. 1991 Aug;86(8):976–980. [PubMed] [Google Scholar]
  14. Fan X. J., Chua A., O'Connell M. A., Kelleher D., Keeling P. W. Interferon-gamma and tumour necrosis factor production in patients with Helicobacter pylori infection. Ir J Med Sci. 1993 Oct;162(10):408–411. doi: 10.1007/BF02996319. [DOI] [PubMed] [Google Scholar]
  15. Ferrero R. L., Thiberge J. M., Kansau I., Wuscher N., Huerre M., Labigne A. The GroES homolog of Helicobacter pylori confers protective immunity against mucosal infection in mice. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6499–6503. doi: 10.1073/pnas.92.14.6499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Forman D., Newell D. G., Fullerton F., Yarnell J. W., Stacey A. R., Wald N., Sitas F. Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. BMJ. 1991 Jun 1;302(6788):1302–1305. doi: 10.1136/bmj.302.6788.1302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gionchetti P., Vaira D., Campieri M., Holton J., Menegatti M., Belluzzi A., Bertinelli E., Ferretti M., Brignola C., Miglioli M. Enhanced mucosal interleukin-6 and -8 in Helicobacter pylori-positive dyspeptic patients. Am J Gastroenterol. 1994 Jun;89(6):883–887. [PubMed] [Google Scholar]
  18. Ilangumaran S., Shanker Narayan N. P., Ramu G., Muthukkaruppan V. R. Cellular and humoral immune responses to recombinant 65-kD antigen of Mycobacterium leprae in leprosy patients and healthy controls. Clin Exp Immunol. 1994 Apr;96(1):79–85. doi: 10.1111/j.1365-2249.1994.tb06234.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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 Mar;83(3):396–400. doi: 10.1111/j.1365-2249.1991.tb05650.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kelso A. Th1 and Th2 subsets: paradigms lost? Immunol Today. 1995 Aug;16(8):374–379. doi: 10.1016/0167-5699(95)80004-2. [DOI] [PubMed] [Google Scholar]
  21. Kiessling R., Grönberg A., Ivanyi J., Söderström K., Ferm M., Kleinau S., Nilsson E., Klareskog L. Role of hsp60 during autoimmune and bacterial inflammation. Immunol Rev. 1991 Jun;121:91–111. doi: 10.1111/j.1600-065x.1991.tb00824.x. [DOI] [PubMed] [Google Scholar]
  22. Kühn R., Löhler J., Rennick D., Rajewsky K., Müller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993 Oct 22;75(2):263–274. doi: 10.1016/0092-8674(93)80068-p. [DOI] [PubMed] [Google Scholar]
  23. Lee A., Fox J., Hazell S. Pathogenicity of Helicobacter pylori: a perspective. Infect Immun. 1993 May;61(5):1601–1610. doi: 10.1128/iai.61.5.1601-1610.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lucey D. R., Clerici M., Shearer G. M. Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clin Microbiol Rev. 1996 Oct;9(4):532–562. doi: 10.1128/cmr.9.4.532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Macchia G., Massone A., Burroni D., Covacci A., Censini S., Rappuoli R. The Hsp60 protein of Helicobacter pylori: structure and immune response in patients with gastroduodenal diseases. Mol Microbiol. 1993 Aug;9(3):645–652. doi: 10.1111/j.1365-2958.1993.tb01724.x. [DOI] [PubMed] [Google Scholar]
  26. Moore K. W., O'Garra A., de Waal Malefyt R., Vieira P., Mosmann T. R. Interleukin-10. Annu Rev Immunol. 1993;11:165–190. doi: 10.1146/annurev.iy.11.040193.001121. [DOI] [PubMed] [Google Scholar]
  27. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  28. Negrini R., Lisato L., Zanella I., Cavazzini L., Gullini S., Villanacci V., Poiesi C., Albertini A., Ghielmi S. Helicobacter pylori infection induces antibodies cross-reacting with human gastric mucosa. Gastroenterology. 1991 Aug;101(2):437–445. doi: 10.1016/0016-5085(91)90023-e. [DOI] [PubMed] [Google Scholar]
  29. Noach L. A., Bosma N. B., Jansen J., Hoek F. J., van Deventer S. J., Tytgat G. N. Mucosal tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8 production in patients with Helicobacter pylori infection. Scand J Gastroenterol. 1994 May;29(5):425–429. doi: 10.3109/00365529409096833. [DOI] [PubMed] [Google Scholar]
  30. Nomura A., Stemmermann G. N., Chyou P. H., Kato I., Perez-Perez G. I., Blaser M. J. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med. 1991 Oct 17;325(16):1132–1136. doi: 10.1056/NEJM199110173251604. [DOI] [PubMed] [Google Scholar]
  31. Perez-Perez G. I., Blaser M. J. Conservation and diversity of Campylobacter pyloridis major antigens. Infect Immun. 1987 May;55(5):1256–1263. doi: 10.1128/iai.55.5.1256-1263.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Perez-Perez G. I., Dworkin B. M., Chodos J. E., Blaser M. J. Campylobacter pylori antibodies in humans. Ann Intern Med. 1988 Jul 1;109(1):11–17. doi: 10.7326/0003-4819-109-1-11. [DOI] [PubMed] [Google Scholar]
  33. Peterson W. L. Helicobacter pylori and peptic ulcer disease. N Engl J Med. 1991 Apr 11;324(15):1043–1048. doi: 10.1056/NEJM199104113241507. [DOI] [PubMed] [Google Scholar]
  34. Pérez-Pérez G. I., Brown W. R., Cover T. L., Dunn B. E., Cao P., Blaser M. J. Correlation between serological and mucosal inflammatory responses to Helicobacter pylori. Clin Diagn Lab Immunol. 1994 May;1(3):325–329. doi: 10.1128/cdli.1.3.325-329.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Roche P. W., Theuvenet W. J., Britton W. J. Cellular immune responses to mycobacterial heat shock proteins in Nepali leprosy patients and controls. Int J Lepr Other Mycobact Dis. 1992 Mar;60(1):36–43. [PubMed] [Google Scholar]
  36. Sharma S. A., Miller G. G., Perez-Perez G. I., Gupta R. S., Blaser M. J. Humoral and cellular immune recognition of Helicobacter pylori proteins are not concordant. Clin Exp Immunol. 1994 Jul;97(1):126–132. doi: 10.1111/j.1365-2249.1994.tb06590.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Singh B., Gupta R. S. Expression of human 60-kD heat shock protein (HSP60 or P1) in Escherichia coli and the development and characterization of corresponding monoclonal antibodies. DNA Cell Biol. 1992 Jul-Aug;11(6):489–496. doi: 10.1089/dna.1992.11.489. [DOI] [PubMed] [Google Scholar]
  38. Strauss R. M., Wang T. C., Kelsey P. B., Compton C. C., Ferraro M. J., Perez-Perez G., Parsonnet J., Blaser M. J. Association of Helicobacter pylori infection with dyspeptic symptoms in patients undergoing gastroduodenoscopy. Am J Med. 1990 Oct;89(4):464–469. doi: 10.1016/0002-9343(90)90377-p. [DOI] [PubMed] [Google Scholar]
  39. Tarkkanen J., Kosunen T. U., Saksela E. Contact of lymphocytes with Helicobacter pylori augments natural killer cell activity and induces production of gamma interferon. Infect Immun. 1993 Jul;61(7):3012–3016. doi: 10.1128/iai.61.7.3012-3016.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Trejdosiewicz L. K., Calabrese A., Smart C. J., Oakes D. J., Howdle P. D., Crabtree J. E., Losowsky M. S., Lancaster F., Boylston A. W. Gamma delta T cell receptor-positive cells of the human gastrointestinal mucosa: occurrence and V region gene expression in Heliobacter pylori-associated gastritis, coeliac disease and inflammatory bowel disease. Clin Exp Immunol. 1991 Jun;84(3):440–444. [PMC free article] [PubMed] [Google Scholar]
  41. Wanidworanun C., Strober W. Predominant role of tumor necrosis factor-alpha in human monocyte IL-10 synthesis. J Immunol. 1993 Dec 15;151(12):6853–6861. [PubMed] [Google Scholar]
  42. Yamamura M., Uyemura K., Deans R. J., Weinberg K., Rea T. H., Bloom B. R., Modlin R. L. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science. 1991 Oct 11;254(5029):277–279. doi: 10.1126/science.254.5029.277. [DOI] [PubMed] [Google Scholar]
  43. Yi Y., Zhong G., Brunham R. C. Continuous B-cell epitopes in Chlamydia trachomatis heat shock protein 60. Infect Immun. 1993 Mar;61(3):1117–1120. doi: 10.1128/iai.61.3.1117-1120.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Yoshida N., Granger D. N., Evans D. J., Jr, Evans D. G., Graham D. Y., Anderson D. C., Wolf R. E., Kvietys P. R. Mechanisms involved in Helicobacter pylori-induced inflammation. Gastroenterology. 1993 Nov;105(5):1431–1440. doi: 10.1016/0016-5085(93)90148-6. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Diagnostic Laboratory Immunology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES