Direct ex vivo kinetic and phenotypic analyses of CD8+ T-cell responses induced by DNA immunization

D. E. Hassett, Mark Slifka, J. Zhang, J. L. Whitton

Research output: Contribution to journalArticle

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Abstract

CD8+ T-cell responses can be induced by DNA immunization, but little is known about the kinetics of these responses in vivo in the absence of restimulation or how soon protective immunity is conferred by a DNA vaccine. It is also unclear if CD8+ T cells primed by DNA vaccines express the vigorous effector functions characteristic of cells primed by natural infection or by immunization with a recombinant live virus vaccine. To address these issues, we have used the sensitive technique of intracellular cytokine staining to carry out direct ex vivo kinetic and phenotypic analyses of antigen-specific CD8+ T cells present in the spleens of mice at various times after (i) a single intramuscular administration of a plasmid expressing the nucleoprotein (NP) gene from lymphocytic choriomeningitis virus (LCMV), (ii) infection by a recombinant vaccinia virus carrying the same protein (vvNP), or (iii) LCMV infection. In addition, we have evaluated the rapidity with which protective immunity against both lethal and sublethal LCMV infections is achieved following DNA vaccination. The CD8+ T-cell response in DNA-vaccinated mice was slightly delayed compared to LCMV or vvNP vaccinees, peaking at 15 days postimmunization. Interestingly, the percentage of antigen-specific CD8+ T cells present in the spleen at day 15 and later time points was similar to that observed following vvNP infection. T cells primed by DNA vaccination or by infection exhibited similar cytokine expression profiles and had similar avidities for an immunodominant cytotoxic T lymphocyte epitope peptide, implying that the responses induced by DNA vaccination differ quantitatively but not qualitatively from those induced by live virus infection. Surprisingly, protection from both lethal and sublethal LCMV infections was conferred within 1 week of DNA vaccination, well before the peak of the CD8+ T-cell response.

Original languageEnglish (US)
Pages (from-to)8286-8291
Number of pages6
JournalJournal of Virology
Volume74
Issue number18
DOIs
StatePublished - 2000
Externally publishedYes

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Lymphocytic choriomeningitis virus
Immunization
immunization
T-lymphocytes
Virus Diseases
T-Lymphocytes
kinetics
DNA
infection
Vaccination
CD8 Antigens
vaccination
DNA Vaccines
recombinant vaccines
lethal genes
Immunity
Spleen
Infection
spleen
cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Direct ex vivo kinetic and phenotypic analyses of CD8+ T-cell responses induced by DNA immunization. / Hassett, D. E.; Slifka, Mark; Zhang, J.; Whitton, J. L.

In: Journal of Virology, Vol. 74, No. 18, 2000, p. 8286-8291.

Research output: Contribution to journalArticle

Hassett, D. E. ; Slifka, Mark ; Zhang, J. ; Whitton, J. L. / Direct ex vivo kinetic and phenotypic analyses of CD8+ T-cell responses induced by DNA immunization. In: Journal of Virology. 2000 ; Vol. 74, No. 18. pp. 8286-8291.
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