Generation, specificity, and function of CD8+ T cells in Trypanosoma cruzi infection

Summary: CD8⁺ T cells are crucial to the control of Trypanosoma cruzi infection and probably act via multiple mechanisms, the most important being the production of interferon‐γ (IFN‐γ). In the absence of CD8⁺ T cells, mice quickly succumb to the infection or develop a more severe chronic disease. Reduced production of IFN‐γ by CD8⁺ T cells is also associated with increased severity of chagasic disease in humans. CD8⁺ T cells in chronic T. cruzi infection are maintained as effector memory cells, undergo rapid expansion, and demonstrate effector functions following re‐exposure to antigen. However, the initial generation of T. cruzi‐specific CD8⁺ T‐cell responses appears to be relatively slow to develop. In addition, the expression of the effector function of the CD8⁺ T cells is compromised in some tissues, particularly in muscle. The targets of effective CD8⁺ T‐cell responses in T. cruzi infection are multiple and varied, and they represent some of the best vaccine candidates described to date. Further analysis of CD8⁺ T cells will provide insight into the disease process in T. cruzi infection and should identify methods to assess and enhance immunity to T. cruzi infection and protection from the symptoms of Chagas' disease.