DISTINCT H-2-COMPLEX CONTROL OF MORTALITY, AND IMMUNE-RESPONSES TO TUBERCULOSIS INFECTION IN VIRGIN AND BCG-VACCINATED MICE

We have studied the impact of distinct haplotypes and of different all eles at specific H-2 loci on: (i) the susceptibility to lethal form of experimental tuberculosis; (ii) the level of DTH to mycobacterial ant igens; (iii) the efficacy of vaccination with bacille Calmette-Guerin (BCG); and (iv) the IgG production and T cell proliferative response t o H37Rv antigens. On the basis of median survival time (MST) following primary inoculation with lethal dose of Mycobacterium tuberculosis, s usceptibility to infection associated with I-A(b) and D(b) alleles, ho st resistance associated with I-A(k) and D(d) alleles. Mice bearing a disease-resistant phenotype also developed a vigorous DTH response. Va ccination with BCG before H37Rv infection significantly prolonged the survival time of both resistant and susceptible animals, except in BIO .M (H-2f) mice. The latter exhibited intermediate resistance to infect ion before but slight decrease in the MST following a high-dose BCG va ccination. Distinct H-2 regulation of susceptibility to lethal infecti on 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 ex pression of the H-2f haplotype was associated with a low DTH response to tuberculin following vaccination and subsequent lethal infection. T he lack of BCG protection against Myco. tuberculosis challenge in B10. M mice associated with the high titre of specific IgG. In addition, th ese mice exhibited a unique ability to respond to 65-kD antigen by bot h IgG synthesis and T cell proliferation.