Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1994 Nov;62(11):4887–4892. doi: 10.1128/iai.62.11.4887-4892.1994

Use of anti-CD4+ hybridoma cells to induce Pneumocystis carinii in mice.

D C McFadden 1, M A Powles 1, J G Smith 1, A M Flattery 1, K Bartizal 1, D M Schmatz 1
PMCID: PMC303203  PMID: 7927769

Abstract

A reduction of peripheral CD4+ cell levels has been correlated with the onset of Pneumocystis carinii pneumonia in AIDS patients. Most in vivo drug discovery and development for P. carinii have been conducted in corticosteroid-treated rats. There is need for the development of new small animal models with more selective methods of immunosuppression. This study outlines a new mouse model in which specific depletion of the CD4+ T-lymphocyte population was achieved by subcutaneous injection of G.K1.5 hybridoma cells into C3HeB/FeJ mice. A significant reduction in splenic CD4+ cells was maintained over a 10-week period following a single injection of cells. Circulating anti-CD4+ antibody was detected throughout the 10-week period in hybridoma-injected mice, while circulating antibody was undetectable 4 weeks after repeated injection of purified monoclonal antibody. There was no significant increase in the CD8+ cell populations of the hybridoma-injected mice. P. carinii cysts increased in the lungs of CD4+ T-cell-depleted mice, with the number of cysts detected comparable to levels in dexamethasone-treated mice. High levels of cysts were detected when CD4+ cell populations in the spleen remained below 5% and decreased when CD4+ populations increased above the 5% level. In mice whose CD4+ population was not reduced below 5%, there was no significant increase in P. carinii cysts detected. This study presents a new mouse model with specific immunosuppression requiring a minimum of animal manipulation for use in discovery and development of potential new therapeutics for P. carinii pneumonia.

Full text

PDF
4887

Selected References

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

  1. Araujo F. G. Depletion of L3T4+ (CD4+) T lymphocytes prevents development of resistance to Toxoplasma gondii in mice. Infect Immun. 1991 May;59(5):1614–1619. doi: 10.1128/iai.59.5.1614-1619.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bartlett M. S., Queener S. F., Durkin M. M., Shaw M. A., Smith J. W. Inoculated mouse model of Pneumocystis carinii infection. Diagn Microbiol Infect Dis. 1992 Feb;15(2):129–134. doi: 10.1016/0732-8893(92)90036-s. [DOI] [PubMed] [Google Scholar]
  3. Beck J. M., Warnock M. L., Kaltreider H. B., Shellito J. E. Host defenses against Pneumocystis carinii in mice selectively depleted of CD4+ lymphocytes. Chest. 1993 Feb;103(2 Suppl):116S–118S. doi: 10.1378/chest.103.2_supplement.116s-a. [DOI] [PubMed] [Google Scholar]
  4. Cantorna M. T., Balish E. Role of CD4+ lymphocytes in resistance to mucosal candidiasis. Infect Immun. 1991 Jul;59(7):2447–2455. doi: 10.1128/iai.59.7.2447-2455.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cenci E., Romani L., Vecchiarelli A., Puccetti P., Bistoni F. Role of L3T4+ lymphocytes in protective immunity to systemic Candida albicans infection in mice. Infect Immun. 1989 Nov;57(11):3581–3587. doi: 10.1128/iai.57.11.3581-3587.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  7. Dialynas D. P., Wilde D. B., Marrack P., Pierres A., Wall K. A., Havran W., Otten G., Loken M. R., Pierres M., Kappler J. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. doi: 10.1111/j.1600-065x.1983.tb01083.x. [DOI] [PubMed] [Google Scholar]
  8. Furuta T., Ueda K., Fujiwara K., Yamanouchi K. Cellular and humoral immune responses of mice subclinically infected with Pneumocystis carinii. Infect Immun. 1985 Feb;47(2):544–548. doi: 10.1128/iai.47.2.544-548.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gomez A. M., Bullock W. E., Taylor C. L., Deepe G. S., Jr Role of L3T4+ T cells in host defense against Histoplasma capsulatum. Infect Immun. 1988 Jul;56(7):1685–1691. doi: 10.1128/iai.56.7.1685-1691.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Harmsen A. G., Stankiewicz M. Requirement for CD4+ cells in resistance to Pneumocystis carinii pneumonia in mice. J Exp Med. 1990 Sep 1;172(3):937–945. doi: 10.1084/jem.172.3.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Huffnagle G. B., Yates J. L., Lipscomb M. F. Immunity to a pulmonary Cryptococcus neoformans infection requires both CD4+ and CD8+ T cells. J Exp Med. 1991 Apr 1;173(4):793–800. doi: 10.1084/jem.173.4.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hughes W. T. Comparison of dosages, intervals, and drugs in the prevention of Pneumocystis carinii pneumonia. Antimicrob Agents Chemother. 1988 May;32(5):623–625. doi: 10.1128/aac.32.5.623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hughes W. T., McNabb P. C., Makres T. D., Feldman S. Efficacy of trimethoprim and sulfamethoxazole in the prevention and treatment of Pneumocystis carinii pneumonitis. Antimicrob Agents Chemother. 1974 Mar;5(3):289–293. doi: 10.1128/aac.5.3.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Phair J., Muñoz A., Detels R., Kaslow R., Rinaldo C., Saah A. The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1. Multicenter AIDS Cohort Study Group. N Engl J Med. 1990 Jan 18;322(3):161–165. doi: 10.1056/NEJM199001183220304. [DOI] [PubMed] [Google Scholar]
  15. Powles M. A., McFadden D. C., Pittarelli L. A., Schmatz D. M. Mouse model for Pneumocystis carinii pneumonia that uses natural transmission to initiate infection. Infect Immun. 1992 Apr;60(4):1397–1400. doi: 10.1128/iai.60.4.1397-1400.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Serikawa T., Kitada K., Muraguchi T., Yamada J. A survey of Pneumocystis carinii infection in research mouse colonies in Japan. Lab Anim Sci. 1991 Oct;41(5):411–414. [PubMed] [Google Scholar]
  17. Shellito J., Suzara V. V., Blumenfeld W., Beck J. M., Steger H. J., Ermak T. H. A new model of Pneumocystis carinii infection in mice selectively depleted of helper T lymphocytes. J Clin Invest. 1990 May;85(5):1686–1693. doi: 10.1172/JCI114621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Shultz L. D., Schweitzer P. A., Hall E. J., Sundberg J. P., Taylor S., Walzer P. D. Pneumocystis carinii pneumonia in scid/scid mice. Curr Top Microbiol Immunol. 1989;152:243–249. doi: 10.1007/978-3-642-74974-2_29. [DOI] [PubMed] [Google Scholar]
  19. Walzer P. D., Kim C. K., Linke M. J., Pogue C. L., Huerkamp M. J., Chrisp C. E., Lerro A. V., Wixson S. K., Hall E., Shultz L. D. Outbreaks of Pneumocystis carinii pneumonia in colonies of immunodeficient mice. Infect Immun. 1989 Jan;57(1):62–70. doi: 10.1128/iai.57.1.62-70.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Walzer P. D., Powell R. D., Jr, Yoneda K. Experimental Pneumocystis carinii pneumonia in different strains of cortisonized mice. Infect Immun. 1979 Jun;24(3):939–947. doi: 10.1128/iai.24.3.939-947.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Walzer P. D., Schnelle V., Armstrong D., Rosen P. P. Nude mouse: a new experimental model for Pneumocystis carinii infection. Science. 1977 Jul 8;197(4299):177–179. doi: 10.1126/science.301657. [DOI] [PubMed] [Google Scholar]
  22. Wilde D. B., Marrack P., Kappler J., Dialynas D. P., Fitch F. W. Evidence implicating L3T4 in class II MHC antigen reactivity; monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines. J Immunol. 1983 Nov;131(5):2178–2183. [PubMed] [Google Scholar]

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

RESOURCES