TRYPANOSOMA CRUZI-INDUCED IMMUNOSUPPRESSION - BLOCKADE OF COSTIMULATORY T-CELL RESPONSES IN INFECTED HOSTS DUE TO DEFECTIVE T-CELL RECEPTOR-CD3 FUNCTIONING

A model of experimental Trypanosoma cruzi murine infection with chemic ally induced metacyclic forms (opossum clone Dm28c) showed a marked st ate of T-cell unresponsiveness during acute phase, but lacked evidence of suppressor cell activity. Spleen cells from infected mice were sup pressed in vitro in responses to T-cell activators concanavalin A, ant i-Thy1 monoclonal antibody (MAb), and anti-CD3 MAb compared with splee n cells from control littermates. Activation with accessory cell-indep endent stimulus provided by immobilized anti-CD3 was defective in sple nic CD4-positive T cells from infected mice, but not in such cells fro m control mice. No evidence of splenic suppressor cell activity was fo und in cell-mixing experiments using nylon-passed T cells from control and infected donors. Kinetic experiments showed that there was a disc rete stage in infection when T cells were already suppressed in respon se to anti-CD3 but still responded to anti-CD69 MAb. In these T cells, immobilized anti-CD3 failed to enhance simultaneous CD69 responses, a lthough anti-CDS enhanced CD69 responses in control T cells from uninf ected donors. These results demonstrate an intrinsic defect in T-cell receptor-mediated T-cell activation, which could be a mechanism genera ting T-cell suppression during infection by T. cruzi.