Infection with Trypanosoma cruzi selectively upregulates B7-2 molecules on macrophages and enhances their costimulatory activity

T-cell-mediated immune responses are essential for protection against infection with the protozoan Trypanosoma cruzi. In this study, we investigated the influence of infection of murine macrophages with T. cruzi on costimulatory signals for T lymphocytes provided by these cells. We demonstrate that bone marrow-derived macrophages (BMMph) selectively and strongly upregulate expression of B7-2 molecules after infection, while the expression of other costimulatory molecules such as B7-1, intercellular adhesion molecule 1, lymphocyte function-associated antigen 3, and heat-stable antigen is not significantly affected. Infection by live trypanosomes was required. As a consequence of the strong B7-2 upregulation, the infected macrophages are able to induce proliferation of splenic CD4+ T cells in the presence of anti-CD3 antibodies with much higher efficiency than uninfected macrophages. Costimulation could be inhibited by an antibody to B7-2. Furthermore, costimulatory activity for established T-cell clones of Th1 and Th2 phenotype was also strongly enhanced in BMMph by infection with T. cruzi. Th1 cells stimulated either via anti-CD3 antibodies or via specific antigen proliferated with higher efficiency in the presence of infected macrophages than in the presence of uninfected cells. BMMph stimulated with gamma interferon (IFN-gamma), expressing elevated levels of B7-2 molecules, are also able to enhance Th1 cell proliferation, which was highest, using macrophages which were infected and in parallel were stimulated with IFN-gamma. Noteworthy, for cloned Th2 cells, the mechanism of costimulation differed, because costimulation of Th2 cells was not dependent on B7-2 upregulation but was due to secretion of interleukin-1alpha. These findings demonstrate that infection of macrophages with T. cruzi transforms the macrophage into a potent costimulatory cell based on the induction of two different costimulatory activities.

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