After two decades of intense investigation, the relative contribution of B or T cells in acquired resistance was clarified (Tarleton et al. 1992, Kumar & Tarleton 1998). Mice with B cell deficiency showed increased mortality rates at late stages of infection, indicating that antibody production, although secondary in importance to cellular immunity, is nonetheless important to acquired resistance as suggested by early studies performed by Krettli and Brener (1982). Interestingly the B cell deficient mice showed a delayed rise in the acute parasitaemia, suggesting that antibodies may actually enhance parasite virulence in early stages of infection. Depending on the isotype and antibody specificities stimulated early in the antibody response, opsonization may occur, thereby enhacing the uptake of the parasite by macrophages (Lages-Silva et al. 1987). At times when macrophage activation is transiently blocked by Th2-type of cytokines (refer to the abortive cycles of amastigote replication, later in this text), opsonization may increase rather than diminish the parasite load. In contrast to B cell knockouts, mice lacking class I or class II MHC-restricted T cells died during the acute phase of the infection with the Brazil strain. Not surprisingly, the infection was even worsened in animals that were deficient in both class I and class II MHC expression. Interestingly, the tissue inflammatory responses were absent in mice with the MHC-II class deficiency and the animals succumbed to infection due to high parasite load. Taken together, these studies have demonstrated that effector CD4+ and CD8+ T cells are critically involved in the acute control of T. cruzi infection. Similar processes may occur in humans, given the evidence that HLA-A2+ chagasic patients (indeterminate form) often display antigen-specific CD8+ CTL in their peripheral blood. The molecular mechanisms of target cell killing was recently investigated in infected mice (Kumar & Tarleton 1998). These authors showed, somewhat unexpectedly, that mice with targeted deletion of genes encoding for perfurin or granzyme B could control T. cruzi (Brazil strain) infection as efficiently as wild type animals. Their data suggest that class I MHC restricted CD8+ T cells may kill T. cruzi infected targets using the Fas/Fas L interaction system, or alternatively engage TNF-a and IFN-g cytokines in this process.
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