Skip to main content
Immunology logoLink to Immunology
. 1996 Sep;89(1):26–33.

Correlation between the kinetics of Th1, Th2 cells and pathology in a murine model of experimental pulmonary tuberculosis.

R Hernández-Pando 1, H Orozcoe 1, A Sampieri 1, L Pavón 1, C Velasquillo 1, J Larriva-Sahd 1, J M Alcocer 1, M V Madrid 1
PMCID: PMC1456655  PMID: 8911136

Abstract

T-helper 1 (Th1) Th2 kinetics were studied by immunohistochemistry and molecular biology techniques (reverse transcriptase polymerase chain reaction. RT PCR, Southern-blot) during the course of pulmonary tuberculosis induced in BALB/c mice by the intratracheal instillation of the live and virulent strain H-37Rv. The histopathological study clearly showed two phases of the disease. The first one was an acute phase which was characterized by inflammatory infiltrate in the alveolar capillary interstitium, blood vessel and bronchial wall with formation of granulomas. In this acute phase which lasted from 1 to 28 days, a clear predominance of Th1 cells was observed, manifested by a high percentage of interleukin-2 (IL-2) positive cells in the inflammatory infiltrate and granulomas demonstrated by immunohistology, as well as a gradual increment of interferon-gamma (INF-gamma) m-RNA. This was followed by a chronic or advanced phase characterized by pneumonia, focal necrosis and fibrosis, with a Th0 balance due to an equivalent proportion of IL-2 and IL-4 positive cells in the lung lesions, that coincided with the highest level of INF-gamma and IL-4 mRNA. The cytofluorometric analysis of bronchial lavage cells, showed a predominance of CD4 T cells during the acute phase and CD8 T lymphocytes in the chronic phase, gamma-delta T lymphocytes showed two peaks, at the beginning (3 days) and at the end (4 months) of the infection. These results suggest that T-lymphocyte subset kinetics and the pattern of cytokines produced in the lung during tuberculosis infection changed over time and correlate with the type and magnitude of tissue injury.

Full text

PDF
26

Images in this article

Selected References

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

  1. Alwan W. H., Kozlowska W. J., Openshaw P. J. Distinct types of lung disease caused by functional subsets of antiviral T cells. J Exp Med. 1994 Jan 1;179(1):81–89. doi: 10.1084/jem.179.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnes P. F., Grisso C. L., Abrams J. S., Band H., Rea T. H., Modlin R. L. Gamma delta T lymphocytes in human tuberculosis. J Infect Dis. 1992 Mar;165(3):506–512. doi: 10.1093/infdis/165.3.506. [DOI] [PubMed] [Google Scholar]
  3. Betz M., Fox B. S. Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines. J Immunol. 1991 Jan 1;146(1):108–113. [PubMed] [Google Scholar]
  4. Chomczynski P. A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques. 1993 Sep;15(3):532-4, 536-7. [PubMed] [Google Scholar]
  5. Fernandez-Botran R., Sanders V. M., Mosmann T. R., Vitetta E. S. Lymphokine-mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells. J Exp Med. 1988 Aug 1;168(2):543–558. doi: 10.1084/jem.168.2.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Follows G. A., Munk M. E., Gatrill A. J., Conradt P., Kaufmann S. H. Gamma interferon and interleukin 2, but not interleukin 4, are detectable in gamma/delta T-cell cultures after activation with bacteria. Infect Immun. 1992 Mar;60(3):1229–1231. doi: 10.1128/iai.60.3.1229-1231.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Grzych J. M., Pearce E., Cheever A., Caulada Z. A., Caspar P., Heiny S., Lewis F., Sher A. Egg deposition is the major stimulus for the production of Th2 cytokines in murine schistosomiasis mansoni. J Immunol. 1991 Feb 15;146(4):1322–1327. [PubMed] [Google Scholar]
  8. Haas W., Pereira P., Tonegawa S. Gamma/delta cells. Annu Rev Immunol. 1993;11:637–685. doi: 10.1146/annurev.iy.11.040193.003225. [DOI] [PubMed] [Google Scholar]
  9. Heinzel F. P., Sadick M. D., Mutha S. S., Locksley R. M. Production of interferon gamma, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7011–7015. doi: 10.1073/pnas.88.16.7011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hernandez-Pando R., Rook G. A. The role of TNF-alpha in T-cell-mediated inflammation depends on the Th1/Th2 cytokine balance. Immunology. 1994 Aug;82(4):591–595. [PMC free article] [PubMed] [Google Scholar]
  11. Holt P. G. Down-regulation of immune responses in the lower respiratory tract: the role of alveolar macrophages. Clin Exp Immunol. 1986 Feb;63(2):261–270. [PMC free article] [PubMed] [Google Scholar]
  12. Inoue T., Yoshikai Y., Matsuzaki G., Nomoto K. Early appearing gamma/delta-bearing T cells during infection with Calmétte Guérin bacillus. J Immunol. 1991 Apr 15;146(8):2754–2762. [PubMed] [Google Scholar]
  13. Jarnagin J. L., Luchsinger D. W. The use of fluorescein diacetate and ethidium bromide as a stain for evaluating viability of mycobacteria. Stain Technol. 1980 Jul;55(4):253–258. doi: 10.3109/10520298009067249. [DOI] [PubMed] [Google Scholar]
  14. Kaufmann S. H., Ladel C. H. Application of knockout mice to the experimental analysis of infections with bacteria and protozoa. Trends Microbiol. 1994 Jul;2(7):235–242. doi: 10.1016/0966-842x(94)90628-9. [DOI] [PubMed] [Google Scholar]
  15. Kemeny D. M., Noble A., Holmes B. J., Diaz-Sanchez D. Immune regulation: a new role for the CD8+ T cell. Immunol Today. 1994 Mar;15(3):107–110. doi: 10.1016/0167-5699(94)90152-X. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Orme I. M., Miller E. S., Roberts A. D., Furney S. K., Griffin J. P., Dobos K. M., Chi D., Rivoire B., Brennan P. J. T lymphocytes mediating protection and cellular cytolysis during the course of Mycobacterium tuberculosis infection. Evidence for different kinetics and recognition of a wide spectrum of protein antigens. J Immunol. 1992 Jan 1;148(1):189–196. [PubMed] [Google Scholar]
  18. Orme I. M., Roberts A. D., Griffin J. P., Abrams J. S. Cytokine secretion by CD4 T lymphocytes acquired in response to Mycobacterium tuberculosis infection. J Immunol. 1993 Jul 1;151(1):518–525. [PubMed] [Google Scholar]
  19. Pietsch K., Ehlers S., Jacobs E. Cytokine gene expression in the lungs of BALB/c mice during primary and secondary intranasal infection with Mycoplasma pneumoniae. Microbiology. 1994 Aug;140(Pt 8):2043–2048. doi: 10.1099/13500872-140-8-2043. [DOI] [PubMed] [Google Scholar]
  20. Rook G. A., Hernandez-Pando R. T cell helper types and endocrines in the regulation of tissue-damaging mechanisms in tuberculosis. Immunobiology. 1994 Oct;191(4-5):478–492. doi: 10.1016/S0171-2985(11)80454-7. [DOI] [PubMed] [Google Scholar]
  21. Rook G. A., Onyebujoh P., Stanford J. L. TH1/TH2 switching and loss of CD4+ T cells in chronic infections: an immunoendocrinological hypothesis not exclusive to HIV. Immunol Today. 1993 Nov;14(11):568–569. doi: 10.1016/0167-5699(93)90190-V. [DOI] [PubMed] [Google Scholar]
  22. Salgame P., Abrams J. S., Clayberger C., Goldstein H., Convit J., Modlin R. L., Bloom B. R. Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science. 1991 Oct 11;254(5029):279–282. doi: 10.1126/science.254.5029.279. [DOI] [PubMed] [Google Scholar]
  23. Sher A., Fiorentino D., Caspar P., Pearce E., Mosmann T. Production of IL-10 by CD4+ T lymphocytes correlates with down-regulation of Th1 cytokine synthesis in helminth infection. J Immunol. 1991 Oct 15;147(8):2713–2716. [PubMed] [Google Scholar]
  24. Sher A., Gazzinelli R. T., Oswald I. P., Clerici M., Kullberg M., Pearce E. J., Berzofsky J. A., Mosmann T. R., James S. L., Morse H. C., 3rd Role of T-cell derived cytokines in the downregulation of immune responses in parasitic and retroviral infection. Immunol Rev. 1992 Jun;127:183–204. doi: 10.1111/j.1600-065x.1992.tb01414.x. [DOI] [PubMed] [Google Scholar]
  25. Surcel H. M., Troye-Blomberg M., Paulie S., Andersson G., Moreno C., Pasvol G., Ivanyi J. Th1/Th2 profiles in tuberculosis, based on the proliferation and cytokine response of blood lymphocytes to mycobacterial antigens. Immunology. 1994 Feb;81(2):171–176. [PMC free article] [PubMed] [Google Scholar]
  26. Sussman G., Wadee A. A. Production of a suppressor factor by CD8+ lymphocytes activated by mycobacterial components. Infect Immun. 1991 Aug;59(8):2828–2835. doi: 10.1128/iai.59.8.2828-2835.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Trinchieri G. Interleukin-12 and its role in the generation of TH1 cells. Immunol Today. 1993 Jul;14(7):335–338. doi: 10.1016/0167-5699(93)90230-I. [DOI] [PubMed] [Google Scholar]
  28. Yamamura M., Uyemura K., Deans R. J., Weinberg K., Rea T. H., Bloom B. R., Modlin R. L. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science. 1991 Oct 11;254(5029):277–279. doi: 10.1126/science.254.5029.277. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES