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 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.

[The isolation and testing of syngeneic anti-idiotypic antibodies against antimycobacterial monoclonal antibodies]. / Poluchenie i ispytanie singennykh antiidiotipicheskikh antitel protiv antimikobakterial'nykh monoklonal'nykh antitel.

Fifteen monoclonal antibodies (MAb) were obtained to cell walls (CW) of M. bovinus-8, two of them were limited specific against human and bovine mycobacteria. One MAb reacted in immunoblotting with a protein having molecular mass of 19.1 kDa. It was also found that all MAb bind with the antigen determinants of mycobacterial proteins. The competitive enzyme immunoassay (EIA) helped reveal that the antigenic determinants "recognized" by two MAb are located in the same area despite the fact that one reacted in immunoblotting with a denatured protein and the other "recognized" only a native antigen in EIA. The syngeneic antiidiotypic (anti-ID) immune response was induced by these MAb in BALB/c mice. The EIA showed the binding of anti-ID-antibodies isolated from mice serum both MAb inducing their synthesis and to antimycobacterial serum antibodies of caws with tuberculosis. Data suggesting a similarity existing between the mycobacterial antigen and anti-ID-antibodies were also obtained in the blast transformation reaction: in M. bovinus antigen stimulation of 8 mice lymph node cells sensitized by anti-ID-antibodies and in the reverse situation when the cells sensitive to KC M. bovinus-8 proliferated in response to stimulation by anti-ID-antibodies.

Regulation of T-cell proliferative responses by cells from solid lung tissue of M. tuberculosis-infected mice.

We have studied proliferative responses to mycobacterial antigen preparation (PPD) and to non-specific stimuli of interstitial cells from the lungs of Mycobacterium tuberculosis-infected CBA mice. PPD-reactive lymphocytes appeared in the lung wall tissue in the course of chronic infection, but their proliferative capacity was totally inhibited by the lung macrophages. The latter were also able to suppress the proliferation of immune lymph node T cells. The mechanism of suppression clearly had two components, one being infection-specific and the other non-specific. Non-specific suppression was mediated mainly by prostaglandin E(PGE), whereas the specific mechanism showed only a weak influence of PGE and depended on the presence of I-J+ Lyt-2- nylon-wool-adherent cells in the responder population. Interstitial lung T or B lymphocytes were not involved in specific suppression.

[Suppression of immune response by lung cells in experimental tuberculosis]. / Supressiia immunnogo otveta kletkami legkogo pri éksperimental'nom tuberkuleze.

In vitro proliferative response of lung cells from mice infected with Mycobacterium tuberculosis H37Rv against PPD and Con A was studied. It was shown that the infected lung contained immune T cells, but their response in vitro was totally inhibited by plastic and nylon wool adherent suppressor cells. The whole population of lung cells from infected, but not intact mice, efficiently suppressed the proliferative response of immune lymph node cells against various antigens (non-specific suppression). The inhibition of response again depended on the presence of plastic adherent lung cells. Our data suggest that at least two suppressor pathways are induced in the course of tuberculosis infection: one being specific for mycobacterial antigens and other non-specific. Both types of suppressor pathways depend on the plastic adherent lung cells from tuberculosis lesion.