Kinetics and Phenotype of Vaccine-Induced CD8⁺ T-Cell Responses to Toxoplasma gondii

• Published in: Infection and Immunity 2009-09, Vol.77 (9), p.3894-3901
• Main Authors: Jordan, Kimberly A, Wilson, Emma H, Tait, Elia D, Fox, Barbara A, Roos, David S, Bzik, David J, Dzierszinski, Florence, Hunter, Christopher A
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Applied microbiology; Biological and medical sciences; CD4 antigen; CD4-Positive T-Lymphocytes - physiology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cytolysis; Cytolytic activity; Cytotoxicity; Cytotoxicity, Immunologic; Fundamental and applied biological sciences. Psychology; g-Interferon; Immunization; Immunophenotyping; Kinetics; Lymphocytes T; Mice; Mice, Inbred C57BL; Microbial Immunity and Vaccines; Microbiology; Ovalbumin; Ovalbumin - immunology; Parasites; Perforin; Protozoan Vaccines - immunology; Toxoplasma - immunology; Toxoplasma gondii; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00024-09

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.