Abstract
We have previously shown that mice vaccinated by injection with J774 macrophage-like tumour cells that expressed Mycobacterium leprae heat-shock protein (hsp) 65 as a transgene had acquired a remarkably high degree of protection against subsequent challenge with virulent M. tuberculosis. We show here that antigen-specific T cells cloned from spleens of such vaccinated animals can transfer a high level of protection to non-vaccinated recipients. The most efficient cells were of T-cell receptor (TCR) alpha beta+ and CD4- CD8+ type and specifically lysed mycobacteria-infected macrophages. These findings are consistent with the importance for protective immunity of engaging the endogenous antigen-presenting pathway to bias the immune response towards a cytolytic action against a mycobacterial antigen that is expressed at the surface of infected macrophages. TCR gamma delta+ and TCR alpha beta+ cells interacted synergistically.
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Selected References
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- Andersen P., Askgaard D., Gottschau A., Bennedsen J., Nagai S., Heron I. Identification of immunodominant antigens during infection with Mycobacterium tuberculosis. Scand J Immunol. 1992 Dec;36(6):823–831. doi: 10.1111/j.1365-3083.1992.tb03144.x. [DOI] [PubMed] [Google Scholar]
- Andersen P., Heron I. Specificity of a protective memory immune response against Mycobacterium tuberculosis. Infect Immun. 1993 Mar;61(3):844–851. doi: 10.1128/iai.61.3.844-851.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheng S. H., Penninger J. M., Ferrick D. A., Molina T. J., Wallace V. A., Mak T. W. Biology of murine gamma delta T cells. Crit Rev Immunol. 1991;11(3-4):145–166. [PubMed] [Google Scholar]
- De Libero G., Flesch I., Kaufmann S. H. Mycobacteria-reactive Lyt-2+ T cell lines. Eur J Immunol. 1988 Jan;18(1):59–66. doi: 10.1002/eji.1830180110. [DOI] [PubMed] [Google Scholar]
- Flynn J. L., Goldstein M. M., Triebold K. J., Koller B., Bloom B. R. Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12013–12017. doi: 10.1073/pnas.89.24.12013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guleria I., Mukherjee R., Kaufmann S. H. In vivo depletion of CD4 and CD8 T lymphocytes impairs Mycobacterium w vaccine-induced protection against M. tuberculosis in mice. Med Microbiol Immunol. 1993 Jul;182(3):129–135. doi: 10.1007/BF00190265. [DOI] [PubMed] [Google Scholar]
- Hussein S., Curtis J., Akuffo H., Turk J. L. Dissociation between delayed-type hypersensitivity and resistance to pathogenic mycobacteria demonstrated by T-cell clones. Infect Immun. 1987 Mar;55(3):564–567. doi: 10.1128/iai.55.3.564-567.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Itohara S., Nakanishi N., Kanagawa O., Kubo R., Tonegawa S. Monoclonal antibodies specific to native murine T-cell receptor gamma delta: analysis of gamma delta T cells during thymic ontogeny and in peripheral lymphoid organs. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5094–5098. doi: 10.1073/pnas.86.13.5094. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaufmann S. H. The cellular immune response to heat shock proteins. Experientia. 1992 Jul 15;48(7):640–643. doi: 10.1007/BF02118309. [DOI] [PubMed] [Google Scholar]
- Koga T., Wand-Württenberger A., DeBruyn J., Munk M. E., Schoel B., Kaufmann S. H. T cells against a bacterial heat shock protein recognize stressed macrophages. Science. 1989 Sep 8;245(4922):1112–1115. doi: 10.1126/science.2788923. [DOI] [PubMed] [Google Scholar]
- Kumararatne D. S., Pithie A. S., Drysdale P., Gaston J. S., Kiessling R., Iles P. B., Ellis C. J., Innes J., Wise R. Specific lysis of mycobacterial antigen-bearing macrophages by class II MHC-restricted polyclonal T cell lines in healthy donors or patients with tuberculosis. Clin Exp Immunol. 1990 Jun;80(3):314–323. doi: 10.1111/j.1365-2249.1990.tb03287.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marks K., Amitai Y., Engelhard D., Kori M., Maayan S. Mycobacterium bovis lymphadenitis complicating BCG immunization in an infant with symptomatic HIV-1 infection. Isr J Med Sci. 1993 Jun-Jul;29(6-7):381–382. [PubMed] [Google Scholar]
- Morita C. T., Verma S., Aparicio P., Martinez C., Spits H., Brenner M. B. Functionally distinct subsets of human gamma/delta T cells. Eur J Immunol. 1991 Dec;21(12):2999–3007. doi: 10.1002/eji.1830211215. [DOI] [PubMed] [Google Scholar]
- Munk M. E., Gatrill A. J., Kaufmann S. H. Target cell lysis and IL-2 secretion by gamma/delta T lymphocytes after activation with bacteria. J Immunol. 1990 Oct 15;145(8):2434–2439. [PubMed] [Google Scholar]
- O'Brien R. L., Happ M. P., Dallas A., Cranfill R., Hall L., Lang J., Fu Y. X., Kubo R., Born W. Recognition of a single hsp-60 epitope by an entire subset of gamma delta T lymphocytes. Immunol Rev. 1991 Jun;121:155–170. doi: 10.1111/j.1600-065x.1991.tb00827.x. [DOI] [PubMed] [Google Scholar]
- Orme I. M., Andersen P., Boom W. H. T cell response to Mycobacterium tuberculosis. J Infect Dis. 1993 Jun;167(6):1481–1497. doi: 10.1093/infdis/167.6.1481. [DOI] [PubMed] [Google Scholar]
- Orme I. M., Collins F. M. Adoptive protection of the Mycobacterium tuberculosis-infected lung. Dissociation between cells that passively transfer protective immunity and those that transfer delayed-type hypersensitivity to tuberculin. Cell Immunol. 1984 Mar;84(1):113–120. doi: 10.1016/0008-8749(84)90082-0. [DOI] [PubMed] [Google Scholar]
- Orme I. M. Induction of nonspecific acquired resistance and delayed-type hypersensitivity, but not specific acquired resistance in mice inoculated with killed mycobacterial vaccines. Infect Immun. 1988 Dec;56(12):3310–3312. doi: 10.1128/iai.56.12.3310-3312.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Orme I. Processing and presentation of mycobacterial antigens: implications for the development of a new improved vaccine for tuberculosis control. Tubercle. 1991 Dec;72(4):250–252. doi: 10.1016/0041-3879(91)90048-w. [DOI] [PubMed] [Google Scholar]
- REES R. J., HART P. D. Analysis of the host-parasite equilibrium in chronic murine tuberculosis by total and viable bacillary counts. Br J Exp Pathol. 1961 Feb;42:83–88. [PMC free article] [PubMed] [Google Scholar]
- Reddy R., Zhou F., Huang L., Carbone F., Bevan M., Rouse B. T. pH sensitive liposomes provide an efficient means of sensitizing target cells to class I restricted CTL recognition of a soluble protein. J Immunol Methods. 1991 Aug 9;141(2):157–163. doi: 10.1016/0022-1759(91)90142-3. [DOI] [PubMed] [Google Scholar]
- Silva C. L., Lowrie D. B. A single mycobacterial protein (hsp 65) expressed by a transgenic antigen-presenting cell vaccinates mice against tuberculosis. Immunology. 1994 Jun;82(2):244–248. [PMC free article] [PubMed] [Google Scholar]
- Spits H., Paliard X., Vandekerckhove Y., van Vlasselaer P., de Vries J. E. Functional and phenotypic differences between CD4+ and CD4- T cell receptor-gamma delta clones from peripheral blood. J Immunol. 1991 Aug 15;147(4):1180–1188. [PubMed] [Google Scholar]
- Weissmann G., Cohen C., Hoffstein S. Introduction of enzymes, by means of liposomes, into non-phagocytic human cells in vitro. Biochim Biophys Acta. 1977 Jul 21;498(1):375–385. doi: 10.1016/0304-4165(77)90276-8. [DOI] [PubMed] [Google Scholar]
- Weltman A. C., Rose D. N. The safety of Bacille Calmette-Guérin vaccination in HIV infection and AIDS. AIDS. 1993 Feb;7(2):149–157. doi: 10.1097/00002030-199302000-00001. [DOI] [PubMed] [Google Scholar]
- Young D. B. Chaperonins and the immune response. Semin Cell Biol. 1990 Feb;1(1):27–35. [PubMed] [Google Scholar]