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. 1992 Mar;60(3):1140–1149. doi: 10.1128/iai.60.3.1140-1149.1992

T lymphocytes mediate protection against Yersinia enterocolitica in mice: characterization of murine T-cell clones specific for Y. enterocolitica.

I B Autenrieth 1, A Tingle 1, A Reske-Kunz 1, J Heesemann 1
PMCID: PMC257605  PMID: 1541529

Abstract

Yersinia enterocolitica is enteropathogenic for humans and rodents, causing intestinal and extraintestinal diseases. The cellular immune response of the infected host has not yet been analyzed in detail. Therefore, we used a parenteral mouse infection model to determine the role of T lymphocytes in immunity against Y. enterocolitica. We report the generation and characterization of Y. enterocolitica-specific T-cell clones isolated from spleens of intravenously infected C57BL/6 mice. The T-cell clones obtained showed the phenotype of helper T cells (L3T4) or cytotoxic T cells (Lyt2). All T-cell clones were positive for the interleukin-2 (IL-2) receptor (Tac antigen, p55 subunit) and were negative for the gamma delta T-cell receptor. L3T4+ clones produced small quantities of IL-2 (less than 1 U/ml) when stimulated with heat-killed Y. enterocolitica, whereas Lyt2+ clones produced no or extremely low levels of IL-2. In contrast to IL-2 production, both L3T4+ and Lyt2+ T-cell clones produced considerable quantities of gamma interferon (500 U/ml). When transferred into nonimmune mice, some of the L3T4+, as well as the Lyt2+, T-cell clones could mediate at least partial protection against a challenge of a lethal dose of Y. enterocolitica. These data demonstrate for the first time the generation and characterization of Y. enterocolitica-specific T-cell clones and provide evidence that T cells may be involved in protection against enteropathogenic Y. enterocolitica.

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Selected References

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  1. Adams D. O., Hamilton T. A. Molecular transductional mechanisms by which IFN gamma and other signals regulate macrophage development. Immunol Rev. 1987 Jun;97:5–27. doi: 10.1111/j.1600-065x.1987.tb00514.x. [DOI] [PubMed] [Google Scholar]
  2. Ahvonen P., Sievers K., Aho K. Arthritis associated with Yersinia enterocolitica infection. Acta Rheumatol Scand. 1969;15(3):232–253. doi: 10.3109/rhe1.1969.15.issue-1-4.32. [DOI] [PubMed] [Google Scholar]
  3. Balligand G., Laroche Y., Cornelis G. Genetic analysis of virulence plasmid from a serogroup 9 Yersinia enterocolitica strain: role of outer membrane protein P1 in resistance to human serum and autoagglutination. Infect Immun. 1985 Jun;48(3):782–786. doi: 10.1128/iai.48.3.782-786.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bliska J. B., Guan K. L., Dixon J. E., Falkow S. Tyrosine phosphate hydrolysis of host proteins by an essential Yersinia virulence determinant. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1187–1191. doi: 10.1073/pnas.88.4.1187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bottone E. J. Yersinia enterocolitica: a panoramic view of a charismatic microorganism. CRC Crit Rev Microbiol. 1977;5(2):211–241. doi: 10.3109/10408417709102312. [DOI] [PubMed] [Google Scholar]
  6. Bouza E., Dominguez A., Meseguer M., Buzon L., Boixeda D., Revillo M. J., de Rafael L., Martinez-Beltran J. Yersinia enterocolitica Septicemia. Am J Clin Pathol. 1980 Oct;74(4):404–409. doi: 10.1093/ajcp/74.4.404. [DOI] [PubMed] [Google Scholar]
  7. Bölin I., Portnoy D. A., Wolf-Watz H. Expression of the temperature-inducible outer membrane proteins of yersiniae. Infect Immun. 1985 Apr;48(1):234–240. doi: 10.1128/iai.48.1.234-240.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Carter P. B. Pathogenecity of Yersinia enterocolitica for mice. Infect Immun. 1975 Jan;11(1):164–170. doi: 10.1128/iai.11.1.164-170.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cornelis G. R., Biot T., Lambert de Rouvroit C., Michiels T., Mulder B., Sluiters C., Sory M. P., Van Bouchaute M., Vanooteghem J. C. The Yersinia yop regulon. Mol Microbiol. 1989 Oct;3(10):1455–1459. doi: 10.1111/j.1365-2958.1989.tb00129.x. [DOI] [PubMed] [Google Scholar]
  10. Cornelis G., Laroche Y., Balligand G., Sory M. P., Wauters G. Yersinia enterocolitica, a primary model for bacterial invasiveness. Rev Infect Dis. 1987 Jan-Feb;9(1):64–87. doi: 10.1093/clinids/9.1.64. [DOI] [PubMed] [Google Scholar]
  11. Cover T. L., Aber R. C. Yersinia enterocolitica. N Engl J Med. 1989 Jul 6;321(1):16–24. doi: 10.1056/NEJM198907063210104. [DOI] [PubMed] [Google Scholar]
  12. Delor I., Kaeckenbeeck A., Wauters G., Cornelis G. R. Nucleotide sequence of yst, the Yersinia enterocolitica gene encoding the heat-stable enterotoxin, and prevalence of the gene among pathogenic and nonpathogenic yersiniae. Infect Immun. 1990 Sep;58(9):2983–2988. doi: 10.1128/iai.58.9.2983-2988.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
  14. Goguen J. D., Walker W. S., Hatch T. P., Yother J. Plasmid-determined cytotoxicity in Yersinia pestis and Yersinia pseudotuberculosis. Infect Immun. 1986 Mar;51(3):788–794. doi: 10.1128/iai.51.3.788-794.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Granfors K., Jalkanen S., von Essen R., Lahesmaa-Rantala R., Isomäki O., Pekkola-Heino K., Merilahti-Palo R., Saario R., Isomäki H., Toivanen A. Yersinia antigens in synovial-fluid cells from patients with reactive arthritis. N Engl J Med. 1989 Jan 26;320(4):216–221. doi: 10.1056/NEJM198901263200404. [DOI] [PubMed] [Google Scholar]
  16. Grützkau A., Hanski C., Hahn H., Riecken E. O. Involvement of M cells in the bacterial invasion of Peyer's patches: a common mechanism shared by Yersinia enterocolitica and other enteroinvasive bacteria. Gut. 1990 Sep;31(9):1011–1015. doi: 10.1136/gut.31.9.1011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Guan K. L., Dixon J. E. Protein tyrosine phosphatase activity of an essential virulence determinant in Yersinia. Science. 1990 Aug 3;249(4968):553–556. doi: 10.1126/science.2166336. [DOI] [PubMed] [Google Scholar]
  18. Hahn H., Kaufmann S. H. The role of cell-mediated immunity in bacterial infections. Rev Infect Dis. 1981 Nov-Dec;3(6):1221–1250. doi: 10.1093/clinids/3.6.1221. [DOI] [PubMed] [Google Scholar]
  19. Hammer M., Zeidler H., Klimsa S., Heesemann J. Yersinia enterocolitica in the synovial membrane of patients with Yersinia-induced arthritis. Arthritis Rheum. 1990 Dec;33(12):1795–1800. doi: 10.1002/art.1780331206. [DOI] [PubMed] [Google Scholar]
  20. Hancock G. E., Schaedler R. W., MacDonald T. T. Multigenic control of resistance to Yersinia enterocolitica in inbred strains of mice. Infect Immun. 1988 Feb;56(2):532–533. doi: 10.1128/iai.56.2.532-533.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hancock G. E., Schaedler R. W., MacDonald T. T. Yersinia enterocolitica infection in resistant and susceptible strains of mice. Infect Immun. 1986 Jul;53(1):26–31. doi: 10.1128/iai.53.1.26-31.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hanski C., Kutschka U., Schmoranzer H. P., Naumann M., Stallmach A., Hahn H., Menge H., Riecken E. O. Immunohistochemical and electron microscopic study of interaction of Yersinia enterocolitica serotype O8 with intestinal mucosa during experimental enteritis. Infect Immun. 1989 Mar;57(3):673–678. doi: 10.1128/iai.57.3.673-678.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hanski C., Naumann M., Grützkau A., Pluschke G., Friedrich B., Hahn H., Riecken E. O. Humoral and cellular defense against intestinal murine infection with Yersinia enterocolitica. Infect Immun. 1991 Mar;59(3):1106–1111. doi: 10.1128/iai.59.3.1106-1111.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Heesemann J., Algermissen B., Laufs R. Genetically manipulated virulence of Yersinia enterocolitica. Infect Immun. 1984 Oct;46(1):105–110. doi: 10.1128/iai.46.1.105-110.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Heesemann J., Gaede K. Mechanisms involved in the pathogenesis of Yersinia infections. Rheumatol Int. 1989;9(3-5):213–217. doi: 10.1007/BF00271883. [DOI] [PubMed] [Google Scholar]
  26. Heesemann J., Gross U., Grüter L. Genetic manipulation of virulence of Yersinia enterocolitica. Contrib Microbiol Immunol. 1987;9:312–316. [PubMed] [Google Scholar]
  27. Heesemann J., Keller C., Morawa R., Schmidt N., Siemens H. J., Laufs R. Plasmids of human strains of Yersinia enterocolitica: molecular relatedness and possible importance for pathogenesis. J Infect Dis. 1983 Jan;147(1):107–115. doi: 10.1093/infdis/147.1.107. [DOI] [PubMed] [Google Scholar]
  28. Heesemann J., Laufs R. Construction of a mobilizable Yersinia enterocolitica virulence plasmid. J Bacteriol. 1983 Aug;155(2):761–767. doi: 10.1128/jb.155.2.761-767.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hermann E., Fleischer B., Mayet W. J., Poralla T., Meyer zum Büschenfelde K. H. Response of synovial fluid T cell clones to Yersinia enterocolitica antigens in patients with reactive Yersinia arthritis. Clin Exp Immunol. 1989 Mar;75(3):365–370. [PMC free article] [PubMed] [Google Scholar]
  30. Hsu H. S. Pathogenesis and immunity in murine salmonellosis. Microbiol Rev. 1989 Dec;53(4):390–409. doi: 10.1128/mr.53.4.390-409.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Isberg R. R. Mammalian cell adhesion functions and cellular penetration of enteropathogenic Yersinia species. Mol Microbiol. 1989 Oct;3(10):1449–1453. doi: 10.1111/j.1365-2958.1989.tb00128.x. [DOI] [PubMed] [Google Scholar]
  32. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  33. KNAPP W. Mesenteric adenitis due to Pasteurella pseudotuberculosis in young people. N Engl J Med. 1958 Oct 16;259(16):776–778. doi: 10.1056/NEJM195810162591606. [DOI] [PubMed] [Google Scholar]
  34. Kapperud G., Namork E., Skurnik M., Nesbakken T. Plasmid-mediated surface fibrillae of Yersinia pseudotuberculosis and Yersinia enterocolitica: relationship to the outer membrane protein YOP1 and possible importance for pathogenesis. Infect Immun. 1987 Sep;55(9):2247–2254. doi: 10.1128/iai.55.9.2247-2254.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Katz J., Michalek S. M., Beagley K. W., Eldridge J. H. Characterization of rat T helper cell clones specific for Bacteroides gingivalis antigen. Infect Immun. 1990 Sep;58(9):2785–2791. doi: 10.1128/iai.58.9.2785-2791.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Killar L. M., Eisenstein T. K. Immunity to Salmonella typhimurium infection in C3H/HeJ and C3H/HeNCrlBR mice: studies with an aromatic-dependent live S. typhimurium strain as a vaccine. Infect Immun. 1985 Mar;47(3):605–612. doi: 10.1128/iai.47.3.605-612.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Laitenen O., Tuuhea J., Ahvonen P. Polyarthritis associated with Yersinia enterocolitica infection. Clinical features and laboratory findings in nine cases with severe joint symptoms. Ann Rheum Dis. 1972 Jan;31(1):34–39. doi: 10.1136/ard.31.1.34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lian C. J., Hwang W. S., Pai C. H. Plasmid-mediated resistance to phagocytosis in Yersinia enterocolitica. Infect Immun. 1987 May;55(5):1176–1183. doi: 10.1128/iai.55.5.1176-1183.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Locksley R. M., Scott P. Helper T-cell subsets in mouse leishmaniasis: induction, expansion and effector function. Immunol Today. 1991 Mar;12(3):A58–A61. doi: 10.1016/S0167-5699(05)80017-9. [DOI] [PubMed] [Google Scholar]
  40. Markham R. B., Goellner J., Pier G. B. In vitro T cell-mediated killing of Pseudomonas aeruginosa. I. Evidence that a lymphokine mediates killing. J Immunol. 1984 Aug;133(2):962–968. [PubMed] [Google Scholar]
  41. Markwell M. A., Haas S. M., Bieber L. L., Tolbert N. E. A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem. 1978 Jun 15;87(1):206–210. doi: 10.1016/0003-2697(78)90586-9. [DOI] [PubMed] [Google Scholar]
  42. Martinez R. J. Plasmid-mediated and temperature-regulated surface properties of Yersinia enterocolitica. Infect Immun. 1983 Sep;41(3):921–930. doi: 10.1128/iai.41.3.921-930.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Miller V. L., Falkow S. Evidence for two genetic loci in Yersinia enterocolitica that can promote invasion of epithelial cells. Infect Immun. 1988 May;56(5):1242–1248. doi: 10.1128/iai.56.5.1242-1248.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Miller V. L., Farmer J. J., 3rd, Hill W. E., Falkow S. The ail locus is found uniquely in Yersinia enterocolitica serotypes commonly associated with disease. Infect Immun. 1989 Jan;57(1):121–131. doi: 10.1128/iai.57.1.121-131.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Miller V. L., Finlay B. B., Falkow S. Factors essential for the penetration of mammalian cells by Yersinia. Curr Top Microbiol Immunol. 1988;138:15–39. [PubMed] [Google Scholar]
  46. Milon G., Titus R. G., Cerottini J. C., Marchal G., Louis J. A. Higher frequency of Leishmania major-specific L3T4+ T cells in susceptible BALB/c as compared with resistant CBA mice. J Immunol. 1986 Feb 15;136(4):1467–1471. [PubMed] [Google Scholar]
  47. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  48. Müller I., Pedrazzini T., Farrell J. P., Louis J. T-cell responses and immunity to experimental infection with leishmania major. Annu Rev Immunol. 1989;7:561–578. doi: 10.1146/annurev.iy.07.040189.003021. [DOI] [PubMed] [Google Scholar]
  49. Nauciel C. Role of CD4+ T cells and T-independent mechanisms in acquired resistance to Salmonella typhimurium infection. J Immunol. 1990 Aug 15;145(4):1265–1269. [PubMed] [Google Scholar]
  50. O'Brien A. D., Metcalf E. S. Control of early Salmonella typhimurium growth in innately Salmonella-resistant mice does not require functional T lymphocytes. J Immunol. 1982 Oct;129(4):1349–1351. [PubMed] [Google Scholar]
  51. Pai C. H., DeStephano L. Serum resistance associated with virulence in Yersinia enterocolitica. Infect Immun. 1982 Feb;35(2):605–611. doi: 10.1128/iai.35.2.605-611.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Pai C. H., Mors V. Production of enterotoxin by Yersinia enterocolitica. Infect Immun. 1978 Mar;19(3):908–911. doi: 10.1128/iai.19.3.908-911.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Paul C., Shalala K., Warren R., Smith R. Adoptive transfer of murine host protection to salmonellosis with T-cell growth factor-dependent, Salmonella-specific T-cell lines. Infect Immun. 1985 Apr;48(1):40–43. doi: 10.1128/iai.48.1.40-43.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Portnoy D. A., Martinez R. J. Role of a plasmid in the pathogenicity of Yersinia species. Curr Top Microbiol Immunol. 1985;118:29–51. doi: 10.1007/978-3-642-70586-1_3. [DOI] [PubMed] [Google Scholar]
  55. Powderly W. G., Schreiber J. R., Pier G. B., Markham R. B. T cells recognizing polysaccharide-specific B cells function as contrasuppressor cells in the generation of T cell immunity to Pseudomonas aeruginosa. J Immunol. 1988 Apr 15;140(8):2746–2752. [PubMed] [Google Scholar]
  56. Rabson A. R., Hallett A. F., Koornhof H. J. Generalized Yersinia enterocolitica infection. J Infect Dis. 1975 Apr;131(4):447–451. doi: 10.1093/infdis/131.4.447. [DOI] [PubMed] [Google Scholar]
  57. Reske-Kunz A. B., Rüde E. Fine specificity of a T cell line reactive to bovine insulin. J Immunol. 1982 Mar;128(3):1252–1255. [PubMed] [Google Scholar]
  58. Rosqvist R., Bölin I., Wolf-Watz H. Inhibition of phagocytosis in Yersinia pseudotuberculosis: a virulence plasmid-encoded ability involving the Yop2b protein. Infect Immun. 1988 Aug;56(8):2139–2143. doi: 10.1128/iai.56.8.2139-2143.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Simonet M., Richard S., Berche P. Electron microscopic evidence for in vivo extracellular localization of Yersinia pseudotuberculosis harboring the pYV plasmid. Infect Immun. 1990 Mar;58(3):841–845. doi: 10.1128/iai.58.3.841-845.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Slade S. J., Langhorne J. Production of interferon-gamma during infection of mice with Plasmodium chabaudi chabaudi. Immunobiology. 1989 Oct;179(4-5):353–365. doi: 10.1016/S0171-2985(89)80041-5. [DOI] [PubMed] [Google Scholar]
  61. Solbach W., Lohoff M., Streck H., Rohwer P., Röllinghoff M. Kinetics of cell-mediated immunity developing during the course of Leishmania major infection in 'healer' and 'non-healer' mice: progressive impairment of response to and generation of interleukin-2. Immunology. 1987 Nov;62(3):485–492. [PMC free article] [PubMed] [Google Scholar]
  62. Toivanen A., Granfors K., Lahesmaa-Rantala R., Leino R., Ståhlberg T., Vuento R. Pathogenesis of Yersinia-triggered reactive arthritis: immunological, microbiological and clinical aspects. Immunol Rev. 1985 Aug;86:47–70. doi: 10.1111/j.1600-065x.1985.tb01137.x. [DOI] [PubMed] [Google Scholar]
  63. Vesikari T., Sundqvist C., Mäki M. Adherence and toxicity of Yersinia enterocolitica 0:3 and 0:9 containing virulence-associated plasmids for various cultured cells. Acta Pathol Microbiol Immunol Scand B. 1983 Apr;91(2):121–127. doi: 10.1111/j.1699-0463.1983.tb00020.x. [DOI] [PubMed] [Google Scholar]
  64. Winblad S. Erythema nodosum associated with infection with Yersinia enterocolitica. Scand J Infect Dis. 1969 May;1(1):11–16. doi: 10.3109/inf.1969.1.issue-1.02. [DOI] [PubMed] [Google Scholar]
  65. de Koning J., Heesemann J., Hoogkamp-Korstanje J. A., Festen J. J., Houtman P. M., van Oijen P. L. Yersinia in intestinal biopsy specimens from patients with seronegative spondyloarthropathy: correlation with specific serum IgA antibodies. J Infect Dis. 1989 Jan;159(1):109–112. doi: 10.1093/infdis/159.1.109. [DOI] [PubMed] [Google Scholar]

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