Evasion of immune responses by Trypanosoma cruzi, the etiological agent of Chagas disease

Infection with the protozoan parasite Trypanosoma cruzi leads to Chagas disease, which affects millions of people in Latin America. Infection with T. cruzi cannot be eliminated by the immune system. A better understanding of immune evasion mechanisms is required in order to develop more effective vaccines. During the acute phase, parasites replicate extensively and release immunomodulatory molecules that delay parasite-specific responses mediated by T cells. This immune evasion allows the parasite to spread in the host. In the chronic phase, parasite evasion relies on its replication strategy of hijacking the TGF-β signaling pathway involved in inflammation and tissue regeneration. In this article, the mechanisms of immune evasion described for T. cruzi are reviewed.

Apoptosis as a cause of T-cell unresponsiveness in experimental Chagas' disease

A murine model of Chagas'disease induced by metacyclic forms of T. cruzi was used to evaluate T-cell function during infection. T-cell unresponsiveness to TcR; CD3 stimulation in vitro and lymphocyte activation in vivo occurred simultaneously. These paradoxical findings ar discussed in the light of recent evidence that mature activated T cells become susceptible to TcR-mediated apoptosis. Activation-induced death in T cells from T. cruzi-infected mice has recently been demonstrated in this model. Evidence that TcR-induced death of activated T cells could be a cause for T-cell unresponsiveness in vitro and in vivo, as well as the possible molecular mechanisms involved, are discussed.

Independent and cooperative bheravior of THY1 and CD3:TcR T cell signalling pathways

Normal resting spleen T lymphocytes form mice were stimulated in vitro by monoclonal antibodies (mAbs) against either Thy1 or CD3:TcR surface protein molecules. Although both mAbs were mitogenic, anti-Thy1 activation generated 5 times more IL2 secretiom than anti-CD3 activation under similar conditions. Priduction of IL-like activity was comparable for both Thy1 and CD3-mediated activation. In addition, non-mitogenic doses of anti-CD3 and anti-Thy1 (0.16microng/ml and 0.0125% ascites, repectively) mAbs induced T cell activation when provided together. These reults indicate that Thy1 signalling cooperates with the CD3:TcR pathway to activate T cells. However, the pathway is also regulated independently since IL2 production is larger when stimulated by anti-Thy1 than anti-CD3mAbs