INFECTION WITH TRYPANOSOMA-CRUZI SELECTIVELY UP-REGULATES 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 inve stigated the influence of infection of murine macrophages with T, cruz i on costimulatory signals for T lymphocytes provided by these cells, We demonstrate that bone marrow-derived macrophages (BMMph) selectivel y 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 anti gen 3, and heat-stable antigen is not significantly affected, Infectio n by live trypanosomes was required, As a consequence of the strong B7 -2 upregulation, the infected macrophages are able to induce prolifera tion of splenic CD4+ T cells in the presence of anti-CD3 antibodies wi th much higher efficiency than uninfected macrophages, Costimulation c ould be inhibited by an antibody to B7-2, Furthermore, costimulatory a ctivity for established T-cell clones of Th1 and Th2 phenotype was als o strongly enhanced in BMMph by infection with T. cruzi. Th1 cells sti mulated either via anti-CD3 antibodies or via specific antigen prolife rated with higher efficiency in the presence of infected macrophages t han in the presence of uninfected cells, BMMph stimulated,vith gamma i nterferon (IFN-gamma), expressing elevated levels of B7-2 molecules, a re also able to enhance Th1 cell proliferation, which was highest, usi ng macrophages,which were infected and in parallel were stimulated wit h IFN-gamma, Noteworthy, for cloned Th2 cells, the mechanism of costim ulation differed, because costimulation of Th2 cells was not dependent on B7-2 upregulation but was due to secretion of interleukin-la. Thes e findings demonstrate that infection of macrophages with T, cruzi tra nsforms the macrophage into a potent costimulatory cell based on the i nduction of two different costimulatory activities.