Abstract
Mice infected with high doses of Mycobacterium bovis BCG (3 X 10(7)) showed a marked impairment of delayed-type hypersensitivity to PPD in vivo, and their splenic T cells failed to proliferate when cultured in vitro with concanavalin A or PPD. However, this state of unresponsiveness could be reversed both in vitro and in vivo by the administration of an interleukin 2 (IL-2)-containing preparation. IL-2 produced spontaneously by the gibbon lymphosarcoma T-cell line MLA-144 and T-cell-conditioned medium from a mixed lymphocyte reaction were able to increase DNA synthesis of splenic T lymphocytes from BCG-immunosuppressed mice cultured with concanavalin A or PPD. Furthermore, BCG-infected mice treated in vivo with at least 100 U of IL-2 showed a positive skin reaction to PPD, and their spleen cells were fully responsive in vitro. The reversal of BCG-induced immunosuppression was not observed when infected mice were injected with IL-2 preparations previously incubated with blast cells, a procedure known to remove IL-2 activity. These results indicate that the basis of BCG-induced unresponsiveness is a deficiency in the production of IL-2 rather than a lack of reactive T cells.
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Selected References
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- Bjune G., Closs O., Barnetson R. S. Early events in the host-parasite relationship and immune response in clinical leprosy: its possible importance for leprosy control. Clin Exp Immunol. 1983 Nov;54(2):289–297. [PMC free article] [PubMed] [Google Scholar]
- Bullock W. E. Anergy and infection. Adv Intern Med. 1976;21:149–173. [PubMed] [Google Scholar]
- Cheever M. A., Greenberg P. D., Fefer A., Gillis S. Augmentation of the anti-tumor therapeutic efficacy of long-term cultured T lymphocytes by in vivo administration of purified interleukin 2. J Exp Med. 1982 Apr 1;155(4):968–980. doi: 10.1084/jem.155.4.968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Colizzi V., Ferluga J., Garreau F., Malkovsky M., Asherson G. L. Suppressor cells induced by BCG release non-specific factors in vitro which inhibit DNA synthesis and interleukin-2 production. Immunology. 1984 Jan;51(1):65–71. [PMC free article] [PubMed] [Google Scholar]
- Colizzi V., Garzelli C., Campa M., Toca L., Falcone G. Role of specific delayed-type hypersensitivity in Pseudomonas aeruginosa-infected mice. Immunology. 1982 Oct;47(2):337–344. [PMC free article] [PubMed] [Google Scholar]
- Colizzi V., Giuntini M., Garzelli C., Campa M., Falcone G. Auto-anti-idiotypic antibodies inhibit T-cell-mediated hypersensitivity in BCG-infected mice. Cell Immunol. 1983 Aug;80(1):205–210. doi: 10.1016/0008-8749(83)90107-7. [DOI] [PubMed] [Google Scholar]
- Collins F. M., Morrison N. E., Montalbine V. Immune response to persistent mycobacterial infection in mice. Infect Immun. 1978 May;20(2):430–438. doi: 10.1128/iai.20.2.430-438.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collins F. M., Watson S. R. Suppressor T-cells in BCG-infected mice. Infect Immun. 1979 Aug;25(2):491–496. doi: 10.1128/iai.25.2.491-496.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Donohue J. H., Rosenberg S. A. The fate of interleukin-2 after in vivo administration. J Immunol. 1983 May;130(5):2203–2208. [PubMed] [Google Scholar]
- Flomenberg N., Welte K., Mertelsmann R., Kernan N., Ciobanu N., Venuta S., Feldman S., Kruger G., Kirkpatrick D., Dupont B. Immunologic effects of interleukin 2 in primary immunodeficiency diseases. J Immunol. 1983 Jun;130(6):2644–2650. [PubMed] [Google Scholar]
- Granelli-Piperno A., Vassalli J. D., Reich E. Purification of murine T cell growth factor. A lymphocyte mitogen with helper activity. J Exp Med. 1981 Aug 1;154(2):422–431. doi: 10.1084/jem.154.2.422. [DOI] [PMC free article] [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]
- Hefeneider S. H., Conlon P. J., Henney C. S., Gillis S. In vivo interleukin 2 administration augments the generation of alloreactive cytolytic T lymphocytes and resident natural killer cells. J Immunol. 1983 Jan;130(1):222–227. [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]
- Lamoureux G., Poisson R. Letter: B.C.G. and immunological anergy. Lancet. 1974 May 18;1(7864):989–990. doi: 10.1016/s0140-6736(74)91296-3. [DOI] [PubMed] [Google Scholar]
- Malkovsky M., Asherson G. L., Stockinger B., Watkins M. C. Nonspecific inhibitor released by T acceptor cells reduces the production of interleukin-2. Nature. 1982 Dec 16;300(5893):652–655. doi: 10.1038/300652a0. [DOI] [PubMed] [Google Scholar]
- Malkovský M., Asherson G. L., Chandler P., Colizzi V., Watkins M. C., Zembala M. Nonspecific inhibitor of DNA synthesis elaborated by T acceptor cells. I. Specific hapten- and I-J-driven liberation of an inhibitor of cell proliferation by Lyt-1-2+ cyclophosphamide-sensitive T acceptor cells armed with a product of Lyt-1+2+-specific suppressor cells. J Immunol. 1983 Feb;130(2):785–790. [PubMed] [Google Scholar]
- Malkovský M., Medawar P., Hunt R., Palmer L., Doré C. A diet enriched in vitamin A acetate or in vivo administration of interleukin-2 can counteract a tolerogenic stimulus. Proc R Soc Lond B Biol Sci. 1984 Feb 22;220(1221):439–445. doi: 10.1098/rspb.1984.0012. [DOI] [PubMed] [Google Scholar]
- Marx J. L. Chemical signals in the immune system. Science. 1983 Sep 30;221(4618):1362–1364. doi: 10.1126/science.6604316. [DOI] [PubMed] [Google Scholar]
- Nakamura R. M., Tokunaga T. Induction of suppressor T cells in delayed-type hypersensitivity to Mycobacterium bovis BCG in low-responder mice. Infect Immun. 1980 May;28(2):331–335. doi: 10.1128/iai.28.2.331-335.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rabin H., Hopkins R. F., 3rd, Ruscetti F. W., Neubauer R. H., Brown R. L., Kawakami T. G. Spontaneous release of a factor with properties of T cell growth factor from a continuous line of primate tumor T cells. J Immunol. 1981 Nov;127(5):1852–1856. [PubMed] [Google Scholar]
- Turcotte R. Evidence for two distinct populations of suppressor cells in the spleens of Mycobacterium bovis BCG-Sensitized mice. Infect Immun. 1981 Nov;34(2):315–322. doi: 10.1128/iai.34.2.315-322.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Turcotte R., Lemieux S. Mechanisms of action of Mycobacterium bovis BCG-induced suppressor cells in mitogen-induced blastogenesis. Infect Immun. 1982 Apr;36(1):263–270. doi: 10.1128/iai.36.1.263-270.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wagner H., Hardt C., Heeg K., Röllinghoff M., Pfizenmaier K. T-cell-derived helper factor allows in vivo induction of cytotoxic T cells in nu/nu mice. Nature. 1980 Mar 20;284(5753):278–278. doi: 10.1038/284278a0. [DOI] [PubMed] [Google Scholar]