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Infection and Immunity, September 2009, p. 3894-3901, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00024-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Kimberly A. Jordan,1 Emma H. Wilson,2 Elia D. Tait,1 Barbara A. Fox,3 David S. Roos,4 David J. Bzik,3 Florence Dzierszinski,5 and Christopher A. Hunter1*

Department of Pathobiology, University of Pennsylvania, 380 South University Ave., Philadelphia, Pennsylvania 19104,1 Division of Biomedical Sciences, University of California, Riverside, 900 University Ave., Riverside, California 92521,2 Department of Microbiology and Immunology, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, New Hampshire 03756,3 Department of Biology, 304B Carolyn Lynch Laboratories, University of Pennsylvania, 433 South University Ave., Philadelphia, Pennsylvania 19104,4 Institute of Parasitology, McGill University, 21111 Lakeshore Road, Sainte-Anne-de-Bellevue, Québec H9X 3V9, Canada5

Received 7 January 2009/ Returned for modification 25 February 2009/ Accepted 4 June 2009

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.

* Corresponding author. Mailing address: Room 313, Hill Pavilion, 380 South University Avenue, Philadelphia, PA 19104-4539. Phone: (215) 573-7772. Fax: (215) 746-2295. E-mail: chunter{at}vet.upenn.edu

{triangledown} Published ahead of print on 15 June 2009.

Editor: J. F. Urban, Jr.

Infection and Immunity, September 2009, p. 3894-3901, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00024-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gigley, J. P., Fox, B. A., Bzik, D. J. (2009). Long-Term Immunity to Lethal Acute or Chronic Type II Toxoplasma gondii Infection Is Effectively Induced in Genetically Susceptible C57BL/6 Mice by Immunization with an Attenuated Type I Vaccine Strain. Infect. Immun. 77: 5380-5388 [Abstract] [Full Text]  


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