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

Authors

Kimberly A. Jordan, University of Pennsylvania
Emma H. Wilson, University of California, Riverside
Elia D. Tait, University of Pennsylvania
Barbara A. Fox, Dartmouth CollegeFollow
David S. Roos, University of Pennsylvania
David J. Bzik, Dartmouth CollegeFollow

Document Type

Article

Publication Date

6-15-2009

Publication Title

Infection and Immunity

Department

Geisel School of Medicine

Abstract

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 CD62L^low, KLRG1⁺, and CD127^low, 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.

DOI

10.1128/IAI.00024-09

Original Citation

Jordan KA, Wilson EH, Tait ED, Fox BA, Roos DS, Bzik DJ, Dzierszinski F, Hunter CA. Kinetics and phenotype of vaccine-induced CD8+ T-cell responses to Toxoplasma gondii. Infect Immun. 2009 Sep;77(9):3894-901. doi: 10.1128/IAI.00024-09. Epub 2009 Jun 15. PMID: 19528214; PMCID: PMC2738025.

Dartmouth Digital Commons Citation

Jordan, Kimberly A.; Wilson, Emma H.; Tait, Elia D.; Fox, Barbara A.; Roos, David S.; and Bzik, David J., "Kinetics and Phenotype of Vaccine-Induced CD8+ T-Cell Responses to Toxoplasma gondii" (2009). Dartmouth Scholarship. 936.
https://digitalcommons.dartmouth.edu/facoa/936