Kinetics and Phenotype of Vaccine-Induced CD8⁺ T-Cell Responses to Toxoplasma gondii
2009
Jordan, Kimberly A. | Wilson, Emma H. | Tait, Elia D. | Fox, Barbara A. | Roos, David S. | Bzik, David J. | Dzierszinski, Florence | Hunter, Chris (Christopher A)
Multiple studies have established that the ability of CD8⁺ T cells to act as cytolytic effectors and produce gamma interferon is important in mediating resistance to the intracellular parasite Toxoplasma gondii. To better understand the generation of the antigen-specific CD8⁺ T-cell responses induced by T. gondii, mice were immunized with replication-deficient parasites that express the model antigen ovalbumin (OVA). Class I tetramers specific for SIINFEKL were used to track the OVA-specific endogenous CD8⁺ T cells. The peak CD8⁺ T-cell response was found at day 10 postimmunization, after which the frequency and numbers of antigen-specific cells declined. Unexpectedly, replication-deficient parasites were found to induce antigen-specific cells with faster kinetics than replicating parasites. The generation of optimal numbers of antigen-specific CD8⁺ effector T cells was found to require CD4⁺ T-cell help. At 7 days following immunization, antigen-specific cells were found to be CD62Llow, KLRG1⁺, and CD127low, and they maintained this phenotype for more than 70 days. Antigen-specific CD8⁺ effector T cells in immunized mice exhibited potent perforin-dependent OVA-specific cytolytic activity in vivo. Perforin-dependent cytolysis appeared to be the major cytolytic mechanism; however, a perforin-independent pathway that was not mediated via Fas-FasL was also detected. This study provides further insight into vaccine-induced cytotoxic T-lymphocyte responses that correlate with protective immunity to T. gondii and identifies a critical role for CD4⁺ T cells in the generation of protective CD8⁺ T-cell responses.
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