Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1975 May;11(5):1110–1121. doi: 10.1128/iai.11.5.1110-1121.1975

Immunogenicity of an aerogenic BCG vaccine in T-cell-depleted and normal mice.

N E Morrison, F M Collins
PMCID: PMC415186  PMID: 123519

Abstract

Aerogenic infection of adult thymectomized, lethally irradiated, bone marrow-reconstituted (THXB) C57B1 times C3H F1 hybrid mice with 1 to 3,000 viable BCG Montreal was followed by an extended period of logarithmic growth to a maximum population of 5 times 10-6 bacilli by day 35. The infection spread to the liver, spleen, and bone marrow with extensive multiplication in all test organs before the growth curves abruptly entered a stationary phase. Up to 30% of the THXB mice eventually died as a result of the ongoing BCG infection. There was no sign of an antimicrobial immune response in the THXB mice analogous to that seen in the control animals beginning about day 30. The THXB mice developed considerable immediate but no delayed hypersensitivity to PPD. Intravenous challenge of the BCG-vaccinated THXB mice with 105 virulent Mycobacterium tuberculosis Erdman indicated that they were as susceptible to the tuberculous challenge as a group of unvaccinated controls. Visible surface lesions developed on the lung 90 days postinfection in the T-cell-depleted host with a sharp rise in counts to 175 per lobe on day 120 followed by a plateau for the remainder of the study. Control mice developed visible lesions about day 50, with 225 lesions per lobe by day 70 and a sharp decline to undetectable levels by day 90. The histopathology of these changes was examined carefully, together with the rate of cellular proliferation (tritiated thymidine uptake) by lung and spleen cells as the BCG infection progressed in the THXB mice. Peak uptake by both organs was depressed during the early stages of the BCG infection in the T-cell-depleted mice, but later the incorporation rates were significantly elevated above control values as the infection progressed.

Full text

PDF
1110

Images in this article

1115Image
on p.1115
1117Image
on p.1117

Selected References

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

  1. Bertalanffy F. D. Respiratory tissue: structure, histophysiology, cytodynamics. II. New approaches and interpretations. Int Rev Cytol. 1964;17:213–297. doi: 10.1016/s0074-7696(08)60408-8. [DOI] [PubMed] [Google Scholar]
  2. COHN M. L., DAVIS C. L., MIDDLEBROOK G. Airborne immunization against tuberculosis. Science. 1958 Nov 21;128(3334):1282–1283. doi: 10.1126/science.128.3334.1282. [DOI] [PubMed] [Google Scholar]
  3. Collins F. M., Congdon C. C., Morrison N. E. Growth of mycobacterium bovis (BCG) in T lymphocyte-depleted mice. Infect Immun. 1975 Jan;11(1):57–64. doi: 10.1128/iai.11.1.57-64.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Collins F. M., Mackaness G. B., Montalbine V., Smith M. M. A comparison of the Steenken minimal inhibitory concentration and the Canetti proportion methods for determining levels of drug resistance in cultures of Mycobacterium tuberculosis. Am Rev Respir Dis. 1968 Aug;98(2):189–200. doi: 10.1164/arrd.1968.98.2.189. [DOI] [PubMed] [Google Scholar]
  5. Collins F. M., Mackaness G. B. The relationship of delayed hypersensitivity to acquired antituberculous immunity. I. Tuberculin sensitivity and resistance to reinfection in BCG-vaccinated mice. Cell Immunol. 1970 Sep;1(3):253–265. doi: 10.1016/0008-8749(70)90047-x. [DOI] [PubMed] [Google Scholar]
  6. Collins F. M., Miller T. E. Growth of a drug-resistant strain of Mycobacterium bovis (BCG) in normal and immunized mice. J Infect Dis. 1969 Nov;120(5):517–533. doi: 10.1093/infdis/120.5.517. [DOI] [PubMed] [Google Scholar]
  7. Collins F. M., Montalbine V. Relative immunogenicity of streptomycin-sensitive and -resistant strains of BCG. Infect Immun. 1973 Sep;8(3):381–387. doi: 10.1128/iai.8.3.381-387.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Collins F. M., Montalbine V. Relative immunogenicity of streptomycin-susceptible and -resistant strains of BCG. II. Effect of the route of inoculation on growth and immunogenicity. Am Rev Respir Dis. 1975 Jan;111(1):43–51. doi: 10.1164/arrd.1975.111.1.43. [DOI] [PubMed] [Google Scholar]
  9. Collins F. M., Wayne L. G., v Montalbine The effect of cultural conditions on the distribution of Mycobacterium tuberculosis in the spleens and lungs of specific pathogen-free mice. Am Rev Respir Dis. 1974 Aug;110(2):147–156. doi: 10.1164/arrd.1974.110.2.147. [DOI] [PubMed] [Google Scholar]
  10. Leu R. W., Eddleston A. L., Hadden J. W., Good R. A. Mechanism of action of migration inhibitory factor (MIF). I. Evidence for a receptor for MIF present on the peritoneal macrophage but not on the alveolar macrophage. J Exp Med. 1972 Sep 1;136(3):589–603. doi: 10.1084/jem.136.3.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. MIDDLEBROOK G. Immunological aspects of airborne infection: reactions to inhaled antigens. Bacteriol Rev. 1961 Sep;25:331–346. doi: 10.1128/br.25.3.331-346.1961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mackaness G. B. Delayed hypersensitivity in lung diseases. Ann N Y Acad Sci. 1974;221:312–316. doi: 10.1111/j.1749-6632.1974.tb28231.x. [DOI] [PubMed] [Google Scholar]
  13. Mackaness G. B. The J. Burns Amberson LECTURE The induction and expression of cell-mediated hypersensitivity in the lung. Am Rev Respir Dis. 1971 Dec;104(6):813–828. doi: 10.1164/arrd.1971.104.6.813. [DOI] [PubMed] [Google Scholar]
  14. North R. J. Importance of thymus-derived lymphocytes in cell-mediated immunity to infection. Cell Immunol. 1973 Apr;7(1):166–176. doi: 10.1016/0008-8749(73)90193-7. [DOI] [PubMed] [Google Scholar]
  15. North R. J., Mackaness G. B., Elliott R. W. The histogenesis of immunologically committed lymphocytes. Cell Immunol. 1972 Apr;3(4):680–694. doi: 10.1016/0008-8749(72)90130-x. [DOI] [PubMed] [Google Scholar]
  16. North R. J., Mackaness G. B. Immunological control of macrophage proliferation in vivo. Infect Immun. 1973 Jul;8(1):68–73. doi: 10.1128/iai.8.1.68-73.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. North R. J. Methyl green-pyronin for staining autoradiographs of hydroxyethyl methacrylate-embedded lymphoid tissue. Stain Technol. 1971 Mar;46(2):59–62. doi: 10.3109/10520297109067823. [DOI] [PubMed] [Google Scholar]
  18. North R. J., Spitalny G. Inflammatory lymphocyte in cell-mediated antibacterial immunity: factors governing the accumulation of mediator T cells in peritoneal exudates. Infect Immun. 1974 Sep;10(3):489–498. doi: 10.1128/iai.10.3.489-498.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. North R. J. The relative importance of blood monocytes and fixed macrophages to the expression of cell-mediated immunity to infection. J Exp Med. 1970 Sep 1;132(3):521–534. doi: 10.1084/jem.132.3.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pinkett M. O., Cowdrey C. R., Nowell P. C. Mixed hematopoietic and pulmonary origin of 'alveolar macrophages' as demonstrated by chromosome markers. Am J Pathol. 1966 May;48(5):859–867. [PMC free article] [PubMed] [Google Scholar]
  21. Truitt G. L., Mackaness G. B. Cell-mediated resistance to aerogenic infection of the lung. Am Rev Respir Dis. 1971 Dec;104(6):829–843. doi: 10.1164/arrd.1971.104.6.829. [DOI] [PubMed] [Google Scholar]

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

RESOURCES