Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1995 May;63(5):1800–1805. doi: 10.1128/iai.63.5.1800-1805.1995

Pseudomonas aeruginosa exoenzyme S induces proliferation of human T lymphocytes.

C H Mody 1, D E Buser 1, R M Syme 1, D E Woods 1
PMCID: PMC173227  PMID: 7537248

Abstract

Pseudomonas aeruginosa is a gram-negative bacterium that is responsible for devastating acute and chronic infections, which include bronchiectasis in cystic fibrosis, nosocomial pneumonia, and infection of burn wounds. Previous studies have demonstrated that these patients have impaired host responses, including cell-mediated immune responses, which are important in anti-Pseudomonas host defense. The P. aeruginosa exoproduct, exoenzyme S, has a number of characteristics which suggest that it might be important in cell-mediated immunity. To determine whether exoenzyme S activates lymphocytes to proliferate, peripheral blood mononuclear cells (PBMC) from normal volunteers were stimulated with purified exoenzyme S, and the lymphocyte response was assessed by measuring [3H]thymidine uptake and by counting the number of cells after various times in culture. Ninety-five percent of healthy adult donors had a lymphocyte response to exoenzyme S. The optimal lymphocyte response occurred on day 7, with 4 x 10(5) PBMC per microtiter well when cells were stimulated with 10 micrograms exoenzyme S per ml. [3H]thymidine uptake correlated with an increase in the number of mononuclear cells, indicating that proliferation occurred. In unseparated PBMC, T cells, and to a lesser extent B cells, proliferated. Purified T cells proliferated, while purified B cells proliferated only after the addition of irradiated T cells. Thus, T lymphocytes are necessary and sufficient for the proliferative response to exoenzyme S. We speculate that exoenzyme S from P. aeruginosa is important in T-lymphocyte-mediated host defense to P. aeruginosa. In strategies to enhance impaired cell-mediated immunity, exoenzyme S should be considered as a potential stimulant.

Full Text

The Full Text of this article is available as a PDF (262.7 KB).

Selected References

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

  1. Chen Y. H., Hancock R. E., Mishell R. I. Mitogenic effects of purified outer membrane proteins from Pseudomonas aeruginosa. Infect Immun. 1980 Apr;28(1):178–184. doi: 10.1128/iai.28.1.178-184.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Coburn J., Gill D. M. ADP-ribosylation of p21ras and related proteins by Pseudomonas aeruginosa exoenzyme S. Infect Immun. 1991 Nov;59(11):4259–4262. doi: 10.1128/iai.59.11.4259-4262.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Freihorst J., Merrick J. M., Ogra P. L. Effect of oral immunization with Pseudomonas aeruginosa on the development of specific antibacterial immunity in the lungs. Infect Immun. 1989 Jan;57(1):235–238. doi: 10.1128/iai.57.1.235-238.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gmelig-Meyling F., UytdeHaag A. G., Ballieux R. E. Human B-cell activation in vitro. T cell-dependent pokeweed mitogen-induced differentiation of blood B lymphocytes. Cell Immunol. 1977 Sep;33(1):156–169. doi: 10.1016/0008-8749(77)90143-5. [DOI] [PubMed] [Google Scholar]
  5. Greaves M., Janossy G., Doenhoff M. Selective triggering of human T and B lymphocytes in vitro by polyclonal mitogens. J Exp Med. 1974 Jul 1;140(1):1–18. doi: 10.1084/jem.140.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Grimwood K., To M., Rabin H. R., Woods D. E. Inhibition of Pseudomonas aeruginosa exoenzyme expression by subinhibitory antibiotic concentrations. Antimicrob Agents Chemother. 1989 Jan;33(1):41–47. doi: 10.1128/aac.33.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Iglewski B. H., Sadoff J., Bjorn M. J., Maxwell E. S. Pseudomonas aeruginosa exoenzyme S: an adenosine diphosphate ribosyltransferase distinct from toxin A. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3211–3215. doi: 10.1073/pnas.75.7.3211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lahat N., Rivlin J., Iancu T. C. Functional immunoregulatory T-cell abnormalities in cystic fibrosis patients. J Clin Immunol. 1989 Jul;9(4):287–295. doi: 10.1007/BF00918660. [DOI] [PubMed] [Google Scholar]
  9. Langford D. T., Hiller J. Prospective, controlled study of a polyvalent pseudomonas vaccine in cystic fibrosis--three year results. Arch Dis Child. 1984 Dec;59(12):1131–1134. doi: 10.1136/adc.59.12.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Legaard P. K., LeGrand R. D., Misfeldt M. L. The superantigen Pseudomonas exotoxin A requires additional functions from accessory cells for T lymphocyte proliferation. Cell Immunol. 1991 Jul;135(2):372–382. doi: 10.1016/0008-8749(91)90282-g. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Markham R. B., Pier G. B., Goellner J. J., Mizel S. B. In vitro T cell-mediated killing of Pseudomonas aeruginosa. II. The role of macrophages and T cell subsets in T cell killing. J Immunol. 1985 Jun;134(6):4112–4117. [PubMed] [Google Scholar]
  13. Markham R. B., Powderly W. G. Exposure of mice to live Pseudomonas aeruginosa generates protective cell-mediated immunity in the absence of an antibody response. J Immunol. 1988 Mar 15;140(6):2039–2045. [PubMed] [Google Scholar]
  14. Misfeldt M. L. Microbial "superantigens". Infect Immun. 1990 Aug;58(8):2409–2413. doi: 10.1128/iai.58.8.2409-2413.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Munster A. M., Winchurch R. A., Birmingham W. J., Keeling P. Longitudinal assay of lymphocyte responsiveness in patients with major burns. Ann Surg. 1980 Dec;192(6):772–775. doi: 10.1097/00000658-198012000-00013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nicas T. I., Frank D. W., Stenzel P., Lile J. D., Iglewski B. H. Role of exoenzyme S in chronic Pseudomonas aeruginosa lung infections. Eur J Clin Microbiol. 1985 Apr;4(2):175–179. doi: 10.1007/BF02013593. [DOI] [PubMed] [Google Scholar]
  17. Nicas T. I., Iglewski B. H. Isolation and characterization of transposon-induced mutants of Pseudomonas aeruginosa deficient in production of exoenzyme S. Infect Immun. 1984 Aug;45(2):470–474. doi: 10.1128/iai.45.2.470-474.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Parmely M. J., Iglewski B. H., Horvat R. T. Identification of the principal T lymphocyte-stimulating antigens of Pseudomonas aeruginosa. J Exp Med. 1984 Nov 1;160(5):1338–1349. doi: 10.1084/jem.160.5.1338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pavlovskis O. R., Pollack M., Callahan L. T., 3rd, Iglewski B. H. Passive protection by antitoxin in experimental Pseudomonas aeruginosa burn infections. Infect Immun. 1977 Dec;18(3):596–602. doi: 10.1128/iai.18.3.596-602.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pennington J. E., Reynolds H. Y., Wood R. E., Robinson R. A., Levine A. S. Use of a Pseudomonas Aeruginosa vaccine in pateints with acute leukemia and cystic fibrosis. Am J Med. 1975 May;58(5):629–636. doi: 10.1016/0002-9343(75)90498-2. [DOI] [PubMed] [Google Scholar]
  21. Pier G. B., Markham R. B. Induction in mice of cell-mediated immunity to Pseudomonas aeruginosa by high molecular weight polysaccharide and vinblastine. J Immunol. 1982 May;128(5):2121–2125. [PubMed] [Google Scholar]
  22. Pier G. B., Takeda S., Grout M., Markham R. B. Immune complexes from immunized mice and infected cystic fibrosis patients mediate murine and human T cell killing of hybridomas producing protective, opsonic antibody to Pseudomonas aeruginosa. J Clin Invest. 1993 Mar;91(3):1079–1087. doi: 10.1172/JCI116265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pier G. B., Thomas D. M. Characterization of the human immune response to a polysaccharide vaccine from Pseudomonas aeruginosa. J Infect Dis. 1983 Aug;148(2):206–213. doi: 10.1093/infdis/148.2.206. [DOI] [PubMed] [Google Scholar]
  24. Pier G. B., Thomas D., Small G., Siadak A., Zweerink H. In vitro and in vivo activity of polyclonal and monoclonal human immunoglobulins G, M, and A against Pseudomonas aeruginosa lipopolysaccharide. Infect Immun. 1989 Jan;57(1):174–179. doi: 10.1128/iai.57.1.174-179.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Porwoll J. M., Gebel H. M., Rodey G. E., Markham R. B. In vitro response of human T cells to Pseudomonas aeruginosa. Infect Immun. 1983 May;40(2):670–674. doi: 10.1128/iai.40.2.670-674.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Powderly W. G., Pier G. B., Markham R. B. T lymphocyte-mediated protection against Pseudomonas aeruginosa infection in granulocytopenic mice. J Clin Invest. 1986 Aug;78(2):375–380. doi: 10.1172/JCI112587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Smart W., Sastry P. A., Paranchych W., Singh B. Mapping of the T-cell recognition sites of Pseudomonas aeruginosa PAK polar pili. Infect Immun. 1988 Jan;56(1):18–23. doi: 10.1128/iai.56.1.18-23.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sorensen R. U., Stern R. C., Polmar S. H. Cellular immunity to bacteria: impairment of in vitro lymphocyte responses to Pseudomonas aeruginosa in cystic fibrosis patients. Infect Immun. 1977 Dec;18(3):735–740. doi: 10.1128/iai.18.3.735-740.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sorensen R. U., Stern R. C., Polmar S. H. Lymphocyte responsiveness to Pseudomonas aeruginosa in cystic fibrosis: Relationship to status of pulmonary disease in sibling pairs. J Pediatr. 1978 Aug;93(2):201–205. doi: 10.1016/s0022-3476(78)80496-x. [DOI] [PubMed] [Google Scholar]
  30. Staugas R. E., Harvey D. P., Ferrante A., Nandoskar M., Allison A. C. Induction of tumor necrosis factor (TNF) and interleukin-1 (IL-1) by Pseudomonas aeruginosa and exotoxin A-induced suppression of lymphoproliferation and TNF, lymphotoxin, gamma interferon, and IL-1 production in human leukocytes. Infect Immun. 1992 Aug;60(8):3162–3168. doi: 10.1128/iai.60.8.3162-3168.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ulmer A. J., Pryjma J., Tarnok Z., Ernst M., Flad H. D. Inhibitory and stimulatory effects of Pseudomonas aeruginosa pyocyanine on human T and B lymphocytes and human monocytes. Infect Immun. 1990 Mar;58(3):808–815. doi: 10.1128/iai.58.3.808-815.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Van Geffel R., Hubert E., Urbain J. Study of helper and suppressor T-cells in cystic fibrosis. Immunol Lett. 1982 Sep;5(3):155–159. doi: 10.1016/0165-2478(82)90101-8. [DOI] [PubMed] [Google Scholar]
  33. Woods D. E., Hwang W. S., Shahrabadi M. S., Que J. U. Alteration of pulmonary structure by Pseudomonas aeruginosa exoenzyme S. J Med Microbiol. 1988 Jun;26(2):133–141. doi: 10.1099/00222615-26-2-133. [DOI] [PubMed] [Google Scholar]
  34. Woods D. E., Que J. U. Purification of Pseudomonas aeruginosa exoenzyme S. Infect Immun. 1987 Mar;55(3):579–586. doi: 10.1128/iai.55.3.579-586.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Woods D. E., Schaffer M. S., Rabin H. R., Campbell G. D., Sokol P. A. Phenotypic comparison of Pseudomonas aeruginosa strains isolated from a variety of clinical sites. J Clin Microbiol. 1986 Aug;24(2):260–264. doi: 10.1128/jcm.24.2.260-264.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Woods D. E., To M., Sokol P. A. Pseudomonas aeruginosa exoenzyme S as a pathogenic determinant in respiratory infections. Antibiot Chemother (1971) 1989;42:27–35. doi: 10.1159/000417600. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES