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Infect. Immun. doi:10.1128/IAI.01245-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

LIMITED ROLE FOR CD4⁺ T-CELL HELP IN THE INTITAL PRIMING OF TRYPANOSOMA CRUZI-SPECIFIC CD8⁺ T CELLS

Department of Cellular Biology and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30502

^* To whom correspondence should be addressed. Email: tarleton{at}cb.uga.edu.

	Abstract

Immune control of the protozoan parasite Trypanosoma cruzi requires the activation of both CD4⁺ and CD8⁺ T cells. We have 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, MHC II-deficient mice were infected with Brazil strain 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 in the absence of CD4⁺ help. However the magnitude of the immunodominant TSKB20-specific CD8⁺ T cell responses detectable using class I MHC-peptide tetramers was consistently lower in blood and spleen of MHC II-deficient mice. Spleen cells from infected MHC II-deficient mice produced IFN after in vitro stimulation with T. cruzi peptides at levels similar to wild type mice and MHC II-deficient mice displayed strong T. cruzi peptide-specific in vivo CTL activity. 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 in these mice.