A heart-specific CD4(+) T-cell line obtained from a chronic chagasic mouseinduces carditis in heart-immunized mice and rejection of normal heart transplants in the absence of Trypanosoma cruzi

To study the role of autoreactive T cells in the pathogenesis of cardiomyop athy in Chagas' disease, we generated a cell line by repeated in vitro anti genic stimulation of purified splenic CD4(+) T lymphocytes from a chronical ly Trypanosoma cruzi-infected mouse. Cells from this line were confirmed to be CD4(+) CD8(-) and proliferated upon stimulation with soluble heart anti gens from different animal species, as well as with T. cruzi antigen, in th e presence of syngeneic feeder cells. In vitro antigen stimulation of the c ell line produced a Th1 cytokine profile, with high levels of IFN gamma and IL-2 and absence of IL-4, IL-5 and IL-10. The cell line also terminated th e beating of fetal heart clusters in vitro when cocultured with irradiated syngeneic normal spleen cells. In situ injection of the cell line into well established heart transplants also induced the cessation of heart beating. Finally, adoptive transfer of the cell line to heart-immunized or T. cruzi -infected BALB/c nude mice caused intense heart inflammation.