T lymphocytes in the control of the infection
The T cell response to T. cruzi exhibits a mixed Th1/Th2/Th17 profile. NK-derived IFN-y and IL-12 produced by DCs and/or macrophages contribute in establishing a type 1 environment, while IL-18 would rather exert an immunomodulatory effect.3,124,125 The CD81 T cell response may develop independently of TLR engagement, IFNs, and CD41 T cell help,126—128 though CD41 T cells allowed to reach CD81 T cell frequency are able to control the infection.122 A role for signals associated with NADPH oxidase activation in macrophages has recently been reported.129
The critical dependence on both CD81 and CD41 T cell-mediated responses for control of acute T. cruzi infection in mouse is unequivocal. , The protective effect of CD41 Th1 cells relates to IFN-y activation of trypanocidal action of macrophages and to their help for inducing CD81 T cells and B cell switch to produce protective Ab isotypes.131 Even if IFN-y released by CD81 T cells also contribute to the control of the infection,132 the main protective function of CD81 T cells is likely related to their cytotoxic properties.127 Of note, human but not mouse CD81 T cells express granulysin, able to kill intracellular amastigotes, at odds with perforin and granzyme.28 Studies of the group of Tarleton have provided a lot of information on CD81 T cells in T. cruzi infection.123,133 The mechanisms underlying the inability to totally eliminate T. cruzi-infected cells are to date not precisely known. Data suggest that TGF-(3, regulatory CD41 T cells, or exhaustion do not play a major role in this, though exhausted CD8 T cells may. In humans, a weakening of
CD8 T cell response can be observed, , 9 likely associated with the expression of inhibitory receptors such as PD-1, CTLA-4, 2B4, CD160, and TIM-3140 and perturbed IL-7/IL-7R T cell signaling in chronically infected patients.141
