Pathogenesis and cellular immunity in experimental murine brucellosis.

Infection of mice with Brucella abortus strain 19 provides a most useful and interesting model in which to study chronic infection with intracellular bacteria. Most strains of mice develop a chronic infection. However, certain strains are better able to handle their infection. Long term bone marrow chimeras showed this to be due to bone marrow derived cells, rather than host physiology, although whether it is due T or B lymphocytes, macrophages or polymorphs is yet to be determined. In vitro treatment of lymphocytes from infected donors showed that the subpopulations transferring protection to naive mice was Thy 1+ 2+ Ia-. i.e. the same T cell which induces cell mediated immunity to Listeria. In vivo injection of an optimal regime of anti Ly1 monoclonal antibody exacerbated infection and removed the population of cells transferring immunity. Sub-optimal amounts of anti-Ly-1 abrogated IgG Brucella agglutinating antibody without affecting bacterial numbers, thus confirming the T dependence of IgG antibody and suggesting that it is not important in recovery from infection. Marked splenomegaly occurred about 3 weeks after infection of the mice. It was transferred by T lymphocytes and involved marked influx of macrophages, increased haemopoiesis, fibrin deposition and fluid in the spleen. Although the macrophages were immunosuppressive in vitro they did not appear to account for chronicity of infection. In seeking to account for this chronicity we have compared a number of aspects of the immune response in chronically infected mice and in mice which were able to control their infection. Although we have ruled out a number of possibilities, we have not yet established the basis of chronicity.