Brucella abortus-induced bovine macrophage-T-lymphocyte collaboration was studied as a prerequisite for the eventual clearance of this infectious organism. Esterase-positive, peripheral blood monocytes functioned as an adherent antigen-presenting cell population. A dual requirement for expression of bacterial antigens in combination with self major histocompatibility complex class II products was required by adherent cells for the activation of T lymphocytes. Comparison of antigen-presenting cell populations that were either trypsinized or nontrypsinized following B. abortus ingestion substantiated the need for phagocytosis and antigen processing. A monoclonal antibody (H4) directed against major histocompatibility complex class II determinants was able to block or, with complement, to abrogate T-lymphoctye responses. Measurement of both proliferation and interleukin 2 production via [3H]thymidine incorporation confirmed specific activation of an enriched T-lymphocyte population. These results indicate that in vivo-primed T lymphocytes of peripheral blood origin recognize phagocytized bacterial components of the facultative intracellular bacterium B. abortus and may contribute to the removal of the bacteria. Furthermore, bovine peripheral blood-adherent cells function as classic antigen-presenting cells, which suggests that macrophages are capable of processing this bacteria. Therefore, any lymphocyte-mediated dysfunction attributable to B. abortus most likely occurs at some point in the cascade of immune events following initial macrophage-T-lymphocyte collaboration.
T-cell activation is dependent on nominal antigen associated with major histocompatibility complex (MHC) class II molecules and interleukin-l (IL-1), both provided by antigen-presenting cells. We have studied the effects of Brucella abortus and recombinant bovine gamma interferon (IFN-y) on bovine macrophage expression of MHC class HI and IL-1 molecules and subsequent T-cell proliferation in response to B. abortus.When peripheral blood mononuclear cells were cocultured with B. abortus and IFN-y, increasing amounts of IFN-y, from l to 100 U/ml, down regulated T-cell proliferation. Expression of MHC class II molecules on macrophages was incr'eased independently by IFN-y or B. abortus treatment. Thus, class II molecule expression was not the cause of down regulation of T-cell proliferation as observed in other systems. However, B. abortus-IFN-y-treated 'macrophages obtained from overnight cultures had minimal membrane IL-1 compared with macrophages treated 'with B. abortus alone. Loss of membrane IL-1 required IFN--y and the o-polysaccharide of the lipopolysaccharide. IFN-,y at 1 U/ml in combination with B. abortus produced a 32% decrease in T-cell response, while IFN-y at 100 U/ml added to B. abortus-treated cultures produced an 82% reduction in T-cell response. Membrane IL-1 levels were not altered when recombinant bovine IFN-a or the rough strain 45/20 of B. abortus, which lacks the o-polysaccharide, was used. Secreted IL-1 levels were unaffected by IFN-y and B. abortus treatment. The addition of recombinant bovine IL-1 (0.001 to 0.1 ng/ml) to B. abortus-and IFN--y-treated cultures failed to provide a signal necessary for T-cell proliferation. These data suggest that membrane IL-1 has a key role in T-cell activation in response to B. abortus. When the o-polysaccharide of B. abortus lipopolysaccharide is combined with IFN--y at an inappropriate time during an immune response, T-cell proliferation is prevented and cannot be restored by the addition of exogenous IL-1.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.