Vγ1 γδ T cells regulate type-1/type-2 immune responses and participate in the resistance to infection and development of heart inflammation in Trypanosoma cruzi-infected BALB/c mice

Many different cell populations or lineages participate in the resistance to Trypanosoma cruzi infection. γδ T cells may also take part in a network of interactions that lead to control of T. cruzi infection with minimal tissue damage by controlling αβ T cell activation, as was previously suggested. However, the γδ T cell population is not homogeneous and its functions might vary, depending on T cell receptor usage or distinct stimulatory conditions. In this study, we show that the in vivo depletion of Vγ1-bearing γδ T cells, prior to the infection of BALB/c mice with the Y strain of T. cruzi, induces an increased susceptibility to the infection with lower amounts of IFN-γ being produced by conventional CD4+ or CD8+ T cells. In addition, the production of IL-4 by spleen T cells in Vγ1-depleted mice was increased and the production of IL-10 remained unchanged. Since Vγ1+ γδ T cell depletion diminished the conversion of naive to memory/activated CD4 T cells and the production of IFN-γ during the acute infection, these cells appear to function as helper cells for conventional CD4+ Th1 cells. Depletion of Vγ1+ cells also reduced the infection-induced inflammatory infiltrate in the heart and skeletal muscle. More importantly, Vγ1+ cells were required for up-regulation of CD40L in CD4+ and CD8+ T cells during infection. These results show that a subset of γδ T cells (Vγ1+), which is an important component of the innate immune response, up-regulates the type 1 arm of the adaptative immune response, during T. cruzi infection.