Abstract
We have studied the impact of distinct haplotypes and of different alleles at specific H-2 loci on: (i) the susceptibility to lethal form of experimental tuberculosis; (ii) the level of DTH to mycobacterial antigens; (iii) the efficacy of vaccination with bacille Calmette-Guérin (BCG); and (iv) the IgG production and T cell proliferative response to H37Rv antigens. On the basis of median survival time (MST) following primary inoculation with lethal dose of Mycobacterium tuberculosis, susceptibility to infection associated with I-Ab and Db alleles, host resistance associated with I-Ak and Dd alleles. Mice bearing a disease-resistant phenotype also developed a vigorous DTH response. Vaccination with BCG before H37Rv infection significantly prolonged the survival time of both resistant and susceptible animals, except in B10.M (H-2f) mice. The latter exhibited intermediate resistance to infection before but slight decrease in the MST following a high-dose BCG vaccination. Distinct H-2 regulation of susceptibility to lethal infection and of BCG vaccination efficacy was confirmed in another relatively resistant H-2f-bearing strain A.CA, in which mortality occurred more rapidly in vaccinated compared with primarily infected animals. The expression of the H-2f haplotype was associated with a low DTH response to tuberculin following vaccination and subsequent lethal infection. The lack of BCG protection against Myco, tuberculosis challenge in B10.M mice associated with the high titre of specific IgG. In addition, these mice exhibited a unique ability to respond to 65-kD antigen by both IgG synthesis and T cell proliferation.
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- Abou-Zeid C., Filley E., Steele J., Rook G. A. A simple new method for using antigens separated by polyacrylamide gel electrophoresis to stimulate lymphocytes in vitro after converting bands cut from Western blots into antigen-bearing particles. J Immunol Methods. 1987 Apr 2;98(1):5–10. doi: 10.1016/0022-1759(87)90429-7. [DOI] [PubMed] [Google Scholar]
- Adu H. O., Curtis J., Turk J. L. Role of the major histocompatibility complex in resistance and granuloma formation in response to Mycobacterium lepraemurium infection. Infect Immun. 1983 May;40(2):720–725. doi: 10.1128/iai.40.2.720-725.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blackwell J. M. Leishmania donovani infection in heterozygous and recombinant H-2 haplotype mice. Immunogenetics. 1983;18(2):101–109. doi: 10.1007/BF00368537. [DOI] [PubMed] [Google Scholar]
- Blackwell J. M., Roberts M. B. Immunomodulation of murine visceral leishmaniasis by administration of monoclonal anti-Ia antibodies: differential effects of anti-I-A vs. anti-I-E antibodies. Eur J Immunol. 1987 Nov;17(11):1669–1672. doi: 10.1002/eji.1830171125. [DOI] [PubMed] [Google Scholar]
- Bretscher P. A. A strategy to improve the efficacy of vaccination against tuberculosis and leprosy. Immunol Today. 1992 Sep;13(9):342–345. doi: 10.1016/0167-5699(92)90168-7. [DOI] [PubMed] [Google Scholar]
- Brett S. J., Ivanyi J. Genetic influences on the immune repertoire following tuberculous infection in mice. Immunology. 1990 Sep;71(1):113–119. [PMC free article] [PubMed] [Google Scholar]
- Brett S., Orrell J. M., Swanson Beck J., Ivanyi J. Influence of H-2 genes on growth of Mycobacterium tuberculosis in the lungs of chronically infected mice. Immunology. 1992 May;76(1):129–132. [PMC free article] [PubMed] [Google Scholar]
- Britt W. J., Chesebro B. H-2D control of recovery from Friend virus leukemia: H-2D region influences the kinetics of the T lymphocyte response to Friend virus. J Exp Med. 1983 Jun 1;157(6):1736–1745. doi: 10.1084/jem.157.6.1736. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buschman E., Apt A. S., Nickonenko B. V., Moroz A. M., Averbakh M. H., Skamene E. Genetic aspects of innate resistance and acquired immunity to mycobacteria in inbred mice. Springer Semin Immunopathol. 1988;10(4):319–336. doi: 10.1007/BF02053844. [DOI] [PubMed] [Google Scholar]
- Closs O., Løvik M., Wigzell H., Taylor B. A. H-2-linked gene(s) influence the granulomatous reaction to viable Mycobacterium lepraemurium in the mouse. Scand J Immunol. 1983 Jul;18(1):59–63. doi: 10.1111/j.1365-3083.1983.tb00836.x. [DOI] [PubMed] [Google Scholar]
- Curtis J., Adu H. O., Turk J. L. H-2 linkage control of resistance to subcutaneous infection with Mycobacterium lepraemurium. Infect Immun. 1982 Nov;38(2):434–439. doi: 10.1128/iai.38.2.434-439.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Curtis J., Akuffo-Adu H., Turk J. L. H-2-linked genes which modify resistance of C57BL/10 mice to subcutaneous infection with Mycobacterium lepraemurium. Infect Immun. 1984 Dec;46(3):635–638. doi: 10.1128/iai.46.3.635-638.1984. [DOI] [PMC free article] [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]
- Douglas-Jones A. G., Watson J. D. Immunity to leprosy. II. Genetic control of murine T cell proliferative responses to Mycobacterium leprae. J Immunol. 1985 Oct;135(4):2824–2828. [PubMed] [Google Scholar]
- Duran L. W., Zeller J. C., Lundy J. K., Chang-Miller A., Krco C. J., David C. S., Pease L. R. Genetic analysis of the H-2D region using a new intra-D-region recombinant mouse strain. J Immunol. 1987 Oct 15;139(8):2818–2824. [PubMed] [Google Scholar]
- Fitzgerald T. J. The Th1/Th2-like switch in syphilitic infection: is it detrimental? Infect Immun. 1992 Sep;60(9):3475–3479. doi: 10.1128/iai.60.9.3475-3479.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gazzinelli R. T., Hakim F. T., Hieny S., Shearer G. M., Sher A. Synergistic role of CD4+ and CD8+ T lymphocytes in IFN-gamma production and protective immunity induced by an attenuated Toxoplasma gondii vaccine. J Immunol. 1991 Jan 1;146(1):286–292. [PubMed] [Google Scholar]
- Good M. F., Miller L. H., Kumar S., Quakyi I. A., Keister D., Adams J. H., Moss B., Berzofsky J. A., Carter R. Limited immunological recognition of critical malaria vaccine candidate antigens. Science. 1988 Oct 28;242(4878):574–577. doi: 10.1126/science.2902690. [DOI] [PubMed] [Google Scholar]
- Hamelin-Bourassa D., Skamene E., Gervais F. Susceptibility to a mouse acquired immunodeficiency syndrome is influenced by the H-2. Immunogenetics. 1989;30(4):266–272. doi: 10.1007/BF02421330. [DOI] [PubMed] [Google Scholar]
- Hansen P. W., Petersen C. M., Povlsen J. V., Kristensen T. Cytotoxic human HLA class II restricted purified protein derivative-reactive T-lymphocyte clones. IV. Analysis of HLA restriction pattern and mycobacterial antigen specificity. Scand J Immunol. 1987 Mar;25(3):295–303. doi: 10.1111/j.1365-3083.1987.tb01075.x. [DOI] [PubMed] [Google Scholar]
- Hany M., Oehen S., Schulz M., Hengartner H., Mackett M., Bishop D. H., Overton H., Zinkernagel R. M. Anti-viral protection and prevention of lymphocytic choriomeningitis or of the local footpad swelling reaction in mice by immunization with vaccinia-recombinant virus expressing LCMV-WE nucleoprotein or glycoprotein. Eur J Immunol. 1989 Mar;19(3):417–424. doi: 10.1002/eji.1830190302. [DOI] [PubMed] [Google Scholar]
- Heinzel F. P., Sadick M. D., Holaday B. J., Coffman R. L., Locksley R. M. Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med. 1989 Jan 1;169(1):59–72. doi: 10.1084/jem.169.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hubbard R. D., Flory C. M., Collins F. M. T-cell immune responses in Mycobacterium avium-infected mice. Infect Immun. 1992 Jan;60(1):150–153. doi: 10.1128/iai.60.1.150-153.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ivanyi J., Sharp K. Control by H-2 genes of murine antibody responses to protein antigens of Mycobacterium tuberculosis. Immunology. 1986 Nov;59(3):329–332. [PMC free article] [PubMed] [Google Scholar]
- Ivanyi J., Sharp K., Jackett P., Bothamley G. Immunological study of the defined constituents of mycobacteria. Springer Semin Immunopathol. 1988;10(4):279–300. doi: 10.1007/BF02053841. [DOI] [PubMed] [Google Scholar]
- Jackett P. S., Bothamley G. H., Batra H. V., Mistry A., Young D. B., Ivanyi J. Specificity of antibodies to immunodominant mycobacterial antigens in pulmonary tuberculosis. J Clin Microbiol. 1988 Nov;26(11):2313–2318. doi: 10.1128/jcm.26.11.2313-2318.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaufmann S. H. CD8+ T lymphocytes in intracellular microbial infections. Immunol Today. 1988 Jun;9(6):168–174. doi: 10.1016/0167-5699(88)91292-3. [DOI] [PubMed] [Google Scholar]
- Kaufmann S. H. Heat shock proteins and the immune response. Immunol Today. 1990 Apr;11(4):129–136. doi: 10.1016/0167-5699(90)90050-j. [DOI] [PubMed] [Google Scholar]
- Kaye P. M., Cooke A., Lund T., Wattie M., Blackwell J. M. Altered course of visceral leishmaniasis in mice expressing transgenic I-E molecules. Eur J Immunol. 1992 Feb;22(2):357–364. doi: 10.1002/eji.1830220211. [DOI] [PubMed] [Google Scholar]
- Kurlander R. J., Shawar S. M., Brown M. L., Rich R. R. Specialized role for a murine class I-b MHC molecule in prokaryotic host defenses. Science. 1992 Jul 31;257(5070):678–679. doi: 10.1126/science.1496381. [DOI] [PubMed] [Google Scholar]
- 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]
- Lillehoj E. P., Myers N. B., Lee D. R., Hansen T. H., Coligan J. E. Structural definition of a family of Ld-like molecules distributed among four of seven haplotypes compared. J Immunol. 1985 Aug;135(2):1271–1275. [PubMed] [Google Scholar]
- Locksley R. M., Scott P. Helper T-cell subsets in mouse leishmaniasis: induction, expansion and effector function. Immunol Today. 1991 Mar;12(3):A58–A61. doi: 10.1016/S0167-5699(05)80017-9. [DOI] [PubMed] [Google Scholar]
- López J. A., Reins H. A., Etges R. J., Button L. L., McMaster W. R., Overath P., Klein J. Genetic control of the immune response in mice to Leishmania mexicana surface protease. J Immunol. 1991 Feb 15;146(4):1328–1334. [PubMed] [Google Scholar]
- Mahrt J. L., Shi Y. F. Murine major histocompatibility complex and immune response to Eimeria falciformis. Infect Immun. 1988 Jan;56(1):270–271. doi: 10.1128/iai.56.1.270-271.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mellor A. L., Antoniou J., Robinson P. J. Structure and expression of genes encoding murine Qa-2 class I antigens. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5920–5924. doi: 10.1073/pnas.82.17.5920. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Milich D. R. Immunogenetic analysis of the immune response to hepatitis B virus antigens. Immunol Ser. 1989;43:523–560. [PubMed] [Google Scholar]
- Miyazawa M., Nishio J., Chesebro B. Genetic control of T cell responsiveness to the Friend murine leukemia virus envelope antigen. Identification of class II loci of the H-2 as immune response genes. J Exp Med. 1988 Nov 1;168(5):1587–1605. doi: 10.1084/jem.168.5.1587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nauciel C., Ronco E., Pla M. Influence of different regions of the H-2 complex on the rate of clearance of Salmonella typhimurium. Infect Immun. 1990 Feb;58(2):573–574. doi: 10.1128/iai.58.2.573-574.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nikonenko B. V., Mezhlumova M. B., Apt A. S., Moroz A. M. Local adoptive transfer of delayed-type hypersensitivity to tuberculin from M. bovis (BCG) infected mice. Folia Biol (Praha) 1989;35(4):255–259. [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]
- Polla B. S., Young D. Heat shock proteins and immunity. Immunol Today. 1989 Dec;10(12):393–394. doi: 10.1016/0167-5699(89)90029-7. [DOI] [PubMed] [Google Scholar]
- Rook G. A., Champion B. R., Steele J., Varey A. M., Stanford J. L. I-A restricted activation by T cell lines of anti-tuberculosis activity in murine macrophages. Clin Exp Immunol. 1985 Feb;59(2):414–420. [PMC free article] [PubMed] [Google Scholar]
- Rubocki R. J., Hansen T. H., Lee D. R. Molecular studies of murine mutant BALB/c-H-2dm2 define a deletion of several class I genes including the entire H-2Ld gene. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9606–9610. doi: 10.1073/pnas.83.24.9606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Singer D. S., Hare J., Golding H., Flaherty L., Rudikoff S. Characterization of a new subfamily of class I genes in the H-2 complex of the mouse. Immunogenetics. 1988;28(1):13–21. doi: 10.1007/BF00372524. [DOI] [PubMed] [Google Scholar]
- Skamene E., Gros P., Forget A., Kongshavn P. A., St Charles C., Taylor B. A. Genetic regulation of resistance to intracellular pathogens. Nature. 1982 Jun 10;297(5866):506–509. doi: 10.1038/297506a0. [DOI] [PubMed] [Google Scholar]
- Stephan D., Sun H., Lindahl K. F., Meyer E., Hämmerling G., Hood L., Steinmetz M. Organization and evolution of D region class I genes in the mouse major histocompatibility complex. J Exp Med. 1986 May 1;163(5):1227–1244. doi: 10.1084/jem.163.5.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wassom D. L., Kelly E. A. The role of the major histocompatibility complex in resistance to parasite infections. Crit Rev Immunol. 1990;10(1):31–52. [PubMed] [Google Scholar]
- Weiss E. H., Golden L., Fahrner K., Mellor A. L., Devlin J. J., Bullman H., Tiddens H., Bud H., Flavell R. A. Organization and evolution of the class I gene family in the major histocompatibility complex of the C57BL/10 mouse. Nature. 1984 Aug 23;310(5979):650–655. doi: 10.1038/310650a0. [DOI] [PubMed] [Google Scholar]

