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

Angel Padilla, Dan Xu, Diana Martin, and Rick Tarleton^*

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

Received 4 August 2006/ Returned for modification 9 September 2006/ Accepted 3 October 2006

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.

Published ahead of print on 16 October 2006.

Editor: J. F. Urban, Jr.

A.P. and D.X. contributed equally to this study.

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