Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1992 Aug 1;176(2):581–586. doi: 10.1084/jem.176.2.581

Evidence for an alpha/beta T cell-independent mechanism of resistance to mycobacteria. Bacillus-Calmette-Guerin causes progressive infection in severe combined immunodeficient mice, but not in nude mice or in mice depleted of CD4+ and CD8+ T cells

PMCID: PMC2119317  PMID: 1354243

Abstract

Depleting thymectomized mice of CD4+ T cells, or CD4+ plus CD8+ T cells, rendered them incapable of resolving Bacillus-Calmette-Guerin (BCG) infection in their lives, spleens, kidneys, and lungs. However, it did not render them incapable of stabilizing infection in the latter three organs after an initial period of BCG growth. Athymic nude mice showed a similar capacity to control BCG growth in these organs after a certain stage of infection. In contrast, congenitally severe combined immunodeficient (SCID) mice appeared to offer no resistance to BCG infection, in that the organism grew progressively in all organs of these mice and was lethal for them beginning on day 55 of infection. The results suggest that, although CD4+ T cells are important for resolving BCG infection, an alpha/beta T cell-independent mechanism of resistance can be acquired at 2-3 wk of infection that is capable of inhibiting further BCG growth in all organs except the lungs. Because this mechanism is absent from SCID mice, it is likely that it depends on the functions of gamma/delta T cells, B cells, or both types of cells. In keeping with this possibility is the additional finding that SCID mice engrafted with lymph node cells depleted of CD4+ or CD8+ T cells were capable of expressing an appreciable level of resistance against BCG infection.

Full Text

The Full Text of this article is available as a PDF (603.5 KB).

Selected References

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

  1. Augustin A., Kubo R. T., Sim G. K. Resident pulmonary lymphocytes expressing the gamma/delta T-cell receptor. Nature. 1989 Jul 20;340(6230):239–241. doi: 10.1038/340239a0. [DOI] [PubMed] [Google Scholar]
  2. Dunn P. L., North R. J. Selective radiation resistance of immunologically induced T cells as the basis for irradiation-induced T-cell-mediated regression of immunogenic tumor. J Leukoc Biol. 1991 Apr;49(4):388–396. doi: 10.1002/jlb.49.4.388. [DOI] [PubMed] [Google Scholar]
  3. Hackett J., Jr, Stebbins C., Rogerson B., Davis M. M., Storb U. Analysis of a T cell receptor gene as a target of the somatic hypermutation mechanism. J Exp Med. 1992 Jul 1;176(1):225–231. doi: 10.1084/jem.176.1.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Janis E. M., Kaufmann S. H., Schwartz R. H., Pardoll D. M. Activation of gamma delta T cells in the primary immune response to Mycobacterium tuberculosis. Science. 1989 May 12;244(4905):713–716. doi: 10.1126/science.2524098. [DOI] [PubMed] [Google Scholar]
  6. Kindred B. Nude mice in immunology. Prog Allergy. 1979;26:137–238. [PubMed] [Google Scholar]
  7. Kishihara K., Yoshikai Y., Matsuzaki G., Mak T. W., Nomoto K. Functional alpha and beta T cell chain receptor messages can be detected in old but not in young athymic mice. Eur J Immunol. 1987 Apr;17(4):477–482. doi: 10.1002/eji.1830170407. [DOI] [PubMed] [Google Scholar]
  8. Kung J. T., Thomas C. A., 3rd Athymic nude CD4+8- T cells produce IL-2 but fail to proliferate in response to mitogenic stimuli. J Immunol. 1988 Dec 1;141(11):3691–3696. [PubMed] [Google Scholar]
  9. Lefford M. J., McGregor D. D., Mackaness G. B. Immune response to Mycobacterium tuberculosis in rats. Infect Immun. 1973 Aug;8(2):182–189. doi: 10.1128/iai.8.2.182-189.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lefford M. J. Transfer of adoptive immunity to tuberculosis in mice. Infect Immun. 1975 Jun;11(6):1174–1181. doi: 10.1128/iai.11.6.1174-1181.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Leveton C., Barnass S., Champion B., Lucas S., De Souza B., Nicol M., Banerjee D., Rook G. T-cell-mediated protection of mice against virulent Mycobacterium tuberculosis. Infect Immun. 1989 Feb;57(2):390–395. doi: 10.1128/iai.57.2.390-395.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Manning D. D., Reed N. D., Shaffer C. F. Maintenance of skin xenografts of widely divergent phylogenetic origin of congenitally athymic (nude) mice. J Exp Med. 1973 Aug 1;138(2):488–494. doi: 10.1084/jem.138.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Matis L. Specificity and selection of gamma-delta receptor-expressing T cells. Immunol Res. 1991;10(1):5–14. doi: 10.1007/BF02918163. [DOI] [PubMed] [Google Scholar]
  14. PIERCE C. H., DUBOS R. J., SCHAEFER W. B. Multiplication and survival of tubercle bacilli in the organs of mice. J Exp Med. 1953 Feb 1;97(2):189–206. doi: 10.1084/jem.97.2.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pedrazzini T., Hug K., Louis J. A. Importance of L3T4+ and Lyt-2+ cells in the immunologic control of infection with Mycobacterium bovis strain bacillus Calmette-Guérin in mice. Assessment by elimination of T cell subsets in vivo. J Immunol. 1987 Sep 15;139(6):2032–2037. [PubMed] [Google Scholar]
  16. Rajasekar R., Sim G. K., Augustin A. Self heat shock and gamma delta T-cell reactivity. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1767–1771. doi: 10.1073/pnas.87.5.1767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sher N. A., Chaparas S. D., Greenberg L. E., Merchant E. B., Vickers J. H. Response of congenitally athymic (nude) mice to infection with Mycobacterium bovis (strain BCG). J Natl Cancer Inst. 1975 Jun;54(6):1419–1426. doi: 10.1093/jnci/54.6.1419. [DOI] [PubMed] [Google Scholar]
  18. Takeya K., Mori R., Nomoto K., Nakayama H. Experimental mycobacterial infections in neonatally thymectomized mice. Am Rev Respir Dis. 1967 Sep;96(3):469–477. doi: 10.1164/arrd.1967.96.3.469. [DOI] [PubMed] [Google Scholar]
  19. Takeya K., Nomoto K., Muraoka S., Shimotori S., Taniguchi T., Miyake T. Growth of two strains of Mycobacterium bovis (BCG) in athymic mice. J Gen Microbiol. 1977 Jun;100(2):403–405. doi: 10.1099/00221287-100-2-403. [DOI] [PubMed] [Google Scholar]
  20. Yoshikai Y., Reis M. D., Mak T. W. Athymic mice express a high level of functional gamma-chain but greatly reduced levels of alpha- and beta-chain T-cell receptor messages. Nature. 1986 Dec 4;324(6096):482–485. doi: 10.1038/324482a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES