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Leistungen
Research leading to improved vaccination to tuberculosis is of major importance, since the disease is a major cause of morbidity and mortality, while the existing vaccine BCG is poorly effective. This project was directed toward the genetic factors and to the association between memory T cell phenotype and protective immunity. Using a murine experimental model following vaccination, the antigenic specificity and the cytokine profile of T cell immunity which is protective against tuberculous challenge have been examined. Investigation of the H-2 complex control of acquired T-cell immunity (magnitude, duration, specificity, T cell phenotype) to mycobacterial antigens was carried out in H-2 congenic tuberculosis-susceptible (C57BL/6), tuberculosis-resistant (4R, B10.D2) and BCG-non-protected (B10.M) mouse strains. The levels of antituberculosis resistance provided by memory immune T cells in BCG protected (CBA) and BCG-non-protected (CBA/N-xid) mouse strains as well as the TB-susceptible I/St strain were examined. Memory T-cells isolated from BCG-vaccinated congenic mouse strains are resistant (B10, CBA) or susceptible to primary tuberculosis (B10M, CBA/N) differences have been found in their phenotypic and functional characteristics. The phenotypic and functional characteristics of T-, B-lymphocytes and magrophages which participate in formation of immunological memory to mycobacteria.
The results obtained include: (i) Genetic mapping and function of non-H-2 genes involved in immune responses to mycobacterial stress proteins (Dr. Ivanyi, London). (ii) Correlation between cytokine responses and vaccine induced protective immunity following challenge of mice with pathogenic tuberculosis. Immunogenicity of Ag85A vaccine in B10 congenic mouse strains with 11 different H2 haplotypes (Dr. Huygen, Brussels). (iii) Analysis of immunological memory following vaccination and tuberculous infection of mice. Cloning of T cells from lungs and lymph nodes. Analysis of polyclonal T cell lines (Dr. Apt, Moscow). (iv) Isolation of memory T cells, analysis of calcium homeostasis in naive and memory T cells and FACS analysis of cellular populations (Dr. Nesmeyanov, Moscow).
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