Kinetics and phenotype of vaccine-induced CD8+ T-cell responses to Toxoplasma gondii.
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.
Jordan
Kimberly A
KA
Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Wilson
Emma H
EH
Tait
Elia D
ED
Fox
Barbara A
BA
Roos
David S
DS
Bzik
David J
DJ
Dzierszinski
Florence
F
Hunter
Christopher A
CA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D007114:Immunization; D016130:Immunophenotyping; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D016052:Protozoan Vaccines / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*
D016052:Protozoan Vaccines; D010047:Ovalbumin