Kinetics and phenotype of vaccine-induced CD8+ T cell responses to Toxoplasma

Infect Immun. 2009 Jun 15. [Epub ahead of print]

Kinetics and phenotype of vaccine-induced CD8+ T cell responses to Toxoplasma gondii

Jordan KA, Wilson EH, Tait ED, Fox BA, Roos DS, Bzik DJ, Dzierszinski F, Hunter CA.

Department of Pathobiology, University of Pennsylvania, 380 South University Ave, Philadelphia, PA 19104, USA; Division of Biomedical Sciences, University of California, Riverside, 900 University Ave, Riverside, CA 92521, USA; Department of Microbiology and Immunology, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, HH 03756; Department of Biology, 304B Carolyn Lynch Laboratories, University of Pennsylvania, 380 South University Ave, Philadelphia, PA 19104, USA; Institute of Parasitology, McGill University, 21111 Lakeshore Road, Sainte-Anne-de-Bellevue, Québec H9X 3V9, Canada.

Multiple studies have established that the ability of CD8(+) T cells to act as cytolytic effectors and produce IFN-gamma 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. 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 post-immunization, 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. 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 CD62L(low), KLRG1(+) and CD127(low), and maintained this phenotype for more than 70 days. Antigen-specific CD8(+) effectors 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 (CTL) 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.

PMID: 19528214 [PubMed - as supplied by publisher]