Abstract
Inbred strain 2 guinea pigs were vaccinated with Mycobacterium bovis BCG or were left unvaccinated. They were maintained for 6 weeks on defined, isocaloric diets containing either 30% (control animals) or 10% (animals receiving low protein) ovalbumin as the sole protein source. Animals were challenged by the respiratory route with a low dose of virulent M. tuberculosis H37Rv and killed 4 weeks later. Protein-malnourished animals were not protected by previous vaccination with BCG. Lymphocytes isolated from various tissues were tested in vitro for proliferative responses to mitogen (concanavalin A) and antigen (purified protein derivative [PPD]), production of interleukin-2 (IL-2), and response to exogenous recombinant IL-2 (rIL-2). Protein-malnourished guinea pigs responded only weakly to PPD skin tests, and their blood and lymph node lymphocytes exhibited impaired proliferation when cultured with PPD in vitro. IL-2 levels were consistently low in cultures of stimulated blood and spleen lymphocytes from protein-deprived animals. BCG vaccination of nutritionally normal guinea pigs, on the other hand, induced significantly more IL-2 production by PPD- and concanavalin A-stimulated lymphocytes. The addition of exogenous mouse rIL-2 (40 and 80 U/ml) in vitro to PPD-stimulated blood and lymph node cells from nonvaccinated, protein-deprived guinea pigs resulted in no improvement of the proliferative response. Previous vaccination of malnourished guinea pigs did not consistently enhance the response of PPD-stimulated lymphocytes to added rIL-2. Dietary protein deficiency and BCG vaccination appear to modulate antigen-driven cellular immunity in animals with tuberculosis by altering the production of, and the response to, IL-2 by PPD-stimulated lymphocytes.
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- Cohen M. K., Bartow R. A., Mintzer C. L., McMurray D. N. Effects of diet and genetics on Mycobacterium bovis BCG vaccine efficacy in inbred guinea pigs. Infect Immun. 1987 Feb;55(2):314–319. doi: 10.1128/iai.55.2.314-319.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Colizzi V. In vivo and in vitro administration of interleukin 2-containing preparation reverses T-cell unresponsiveness in Mycobacterium bovis BCG-infected mice. Infect Immun. 1984 Jul;45(1):25–28. doi: 10.1128/iai.45.1.25-28.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Colizzi V., Malkovsky M. Augmentation of interleukin-2 production and delayed hypersensitivity in mice infected with Mycobacterium bovis and fed a diet supplemented with vitamin A acetate. Infect Immun. 1985 May;48(2):581–583. doi: 10.1128/iai.48.2.581-583.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
- Gillis S., Watson J. Interleukin-2 dependent culture of cytolytic T cell lines. Immunol Rev. 1981;54:81–109. doi: 10.1111/j.1600-065x.1981.tb00435.x. [DOI] [PubMed] [Google Scholar]
- Haregewoin A., Godal T., Mustafa A. S., Belehu A., Yemaneberhan T. T-cell conditioned media reverse T-cell unresponsiveness in lepromatous leprosy. Nature. 1983 May 26;303(5915):342–344. doi: 10.1038/303342a0. [DOI] [PubMed] [Google Scholar]
- Hoffenbach A., Bach M. A. Bacillary growth, interleukin 2 production defect, and specific antibody secretion governed by different genetical factors in mice infected subcutaneously with Mycobacterium lepraemurium. Cell Immunol. 1986 Oct 15;102(2):273–286. doi: 10.1016/0008-8749(86)90421-1. [DOI] [PubMed] [Google Scholar]
- Hoffenbach A., Lagrange P. H., Bach M. A. Deficit of interleukin 2 production associated with impaired T-cell proliferative responses in Mycobacterium lepraemurium infection. Infect Immun. 1983 Jan;39(1):109–116. doi: 10.1128/iai.39.1.109-116.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kleinhenz M. E., Ellner J. J. Antigen responsiveness during tuberculosis: regulatory interactions of T cell subpopulations and adherent cells. J Lab Clin Med. 1987 Jul;110(1):31–40. [PubMed] [Google Scholar]
- Lafferty K. J., Prowse S. J., Al-Adra A., Warren H. S., Vasalli J., Reich E. An improved assay for interleukin 2 (lymphocyte growth factor) produced by mitogen-activated lymphocytes. Aust J Exp Biol Med Sci. 1980 Dec;58(6):533–544. doi: 10.1038/icb.1980.55. [DOI] [PubMed] [Google Scholar]
- McMurray D. N., Carlomagno M. A., Mintzer C. L., Tetzlaff C. L. Mycobacterium bovis BCG vaccine fails to protect protein-deficient guinea pigs against respiratory challenge with virulent Mycobacterium tuberculosis. Infect Immun. 1985 Nov;50(2):555–559. doi: 10.1128/iai.50.2.555-559.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McMurray D. N. Cell-mediated immunity in nutritional deficiency. Prog Food Nutr Sci. 1984;8(3-4):193–228. [PubMed] [Google Scholar]
- McMurray D. N., Kimball M. S., Tetzlaff C. L., Mintzer C. L. Effects of protein deprivation and BCG vaccination on alveolar macrophage function in pulmonary tuberculosis. Am Rev Respir Dis. 1986 Jun;133(6):1081–1085. doi: 10.1164/arrd.1986.133.6.1081. [DOI] [PubMed] [Google Scholar]
- McMurray D. N., Mintzer C. L., Tetzlaff C. L., Carlomagno M. A. The influence of dietary protein on the protective effect of BCG in guinea pigs. Tubercle. 1986 Mar;67(1):31–39. doi: 10.1016/0041-3879(86)90029-2. [DOI] [PubMed] [Google Scholar]
- McMurray D. N., Yetley E. A. Cell-mediated immunity in malnourished guinea pigs after Mycobacterium bovis BCG vaccination. Infect Immun. 1982 Mar;35(3):909–914. doi: 10.1128/iai.35.3.909-914.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McMurray D. N., Yetley E. A. Response to Mycobacterium bovis BCG vaccination in protein- and zinc-deficient guinea pigs. Infect Immun. 1983 Feb;39(2):755–761. doi: 10.1128/iai.39.2.755-761.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mohagheghpour N., Gelber R. H., Larrick J. W., Sasaki D. T., Brennan P. J., Engleman E. G. Defective cell-mediated immunity in leprosy: failure of T cells from lepromatous leprosy patients to respond to Mycobacterium leprae is associated with defective expression of interleukin 2 receptors and is not reconstituted by interleukin 2. J Immunol. 1985 Aug;135(2):1443–1449. [PubMed] [Google Scholar]
- Saxena Q. B., Saxena R. K., Adler W. H. Effect of protein calorie malnutrition on the levels of natural and inducible cytotoxic activities in mouse spleen cells. Immunology. 1984 Apr;51(4):727–733. [PMC free article] [PubMed] [Google Scholar]
- Shiratsuchi H., Okuda Y., Tsuyuguchi I. Recombinant human interleukin-2 reverses in vitro-deficient cell-mediated immune responses to tuberculin purified protein derivative by lymphocytes of tuberculous patients. Infect Immun. 1987 Sep;55(9):2126–2131. doi: 10.1128/iai.55.9.2126-2131.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith K. A. Interleukin-2: inception, impact, and implications. Science. 1988 May 27;240(4856):1169–1176. doi: 10.1126/science.3131876. [DOI] [PubMed] [Google Scholar]
- Toossi Z., Kleinhenz M. E., Ellner J. J. Defective interleukin 2 production and responsiveness in human pulmonary tuberculosis. J Exp Med. 1986 May 1;163(5):1162–1172. doi: 10.1084/jem.163.5.1162. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Turcotte R. A suppressor B lymphocyte inhibiting IL-2 consumption in spleen cell cultures from Mycobacterium bovis BCG-infected mice. Immunology. 1987 Nov;62(3):439–444. [PMC free article] [PubMed] [Google Scholar]
- Turcotte R., Legault D. Mechanisms underlying the depressed production of interleukin-2 in spleen and lymph node cell cultures of mice infected with Mycobacterium bovis BCG. Infect Immun. 1986 Mar;51(3):826–831. doi: 10.1128/iai.51.3.826-831.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wiegeshaus E. H., McMurray D. N., Grover A. A., Harding G. E., Smith D. W. Host-parasite relationships in experimental airborne tuberculosis. 3. Relevance of microbial enumeration to acquired resistance in guinea pigs. Am Rev Respir Dis. 1970 Sep;102(3):422–429. doi: 10.1164/arrd.1970.102.3.422. [DOI] [PubMed] [Google Scholar]