Limited Role for CD4 + T-Cell Help in the Initial Priming of Trypanosoma cruzi- Specific CD8 + T Cells

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Abstract
Immune control of the protozoan parasite Trypanosoma cruzi requires the activation of both CD4 + and CD8 + T cells. We recently identified two T. cruzi trans -sialidase peptides that are targets of approximately 30% of all CD8 + T cells during acute T. cruzi infection in mice. To determine whether CD4 + T cells are required for generation of these dominant CD8 + T-cell responses, major histocompatibility complex class II (MHC II)-deficient mice were infected with the Brazil strain of T. cruzi and examined for the generation of antigen-specific CD8 + T cells. Strong trans -sialidase TSKB18- and TSKB20-specific CD8 + T-cell responses were generated in both the presence and the absence of CD4 + help. However, the magnitudes of the immunodominant TSKB20-specific CD8 + T-cell responses detectable using class I MHC-peptide tetramers were consistently lower in the blood and spleens of MHC II-deficient mice. Spleen cells from infected MHC II-deficient mice produced gamma interferon after in vitro stimulation with T. cruzi peptides at levels similar to those in wild-type mice, and MHC II-deficient mice displayed strong T. cruzi peptide-specific cytotoxic T-lymphocyte activity in vivo. Thus, primary CD8 + T-cell responses in experimental T. cruzi infection are generated in the absence of CD4 + T cells, providing further evidence that T. cruzi directly activates and licenses antigen-presenting cells. Nevertheless, unhelped CD8 + T cells in T. cruzi- infected mice fail to reach the frequencies achieved in the presence of CD4 T-cell help and are unable to prevent acute-phase death of these mice.