Incomplete effector/memory differentiation of antigen-primed CD8+ T cells in gene gun DNA-vaccinated mice
Research output: Contribution to journal › Journal article › Research › peer-review
DNA vaccination is an efficient way to induce CD8+ T cell memory, but it is still unclear to what extent such memory responses afford protection in vivo. To study this, we induced CD8+ memory responses directed towards defined viral epitopes, using DNA vaccines encoding immunodominant MHC class I-restricted epitopes of lymphocytic choriomeningitis virus covalently linked to beta2-microglobulin. This vaccine construct primed for a stronger recall response than did a more conventional minigene construct. Despite this, vaccinated mice were only protected against systemic infection whereas protection against the consequences of peripheral challenge was limited. Phenotypic analysis revealed that DNA vaccine-primed CD8+ T cells in uninfected mice differed from virus-primed CD8+ T cells particularly regarding expression of very-late antigen (VLA)-4, an adhesion molecule important for targeting T cells to inflammatory sites. Thus, our DNA vaccine induces a long-lived memory CD8+ T cell population that provides efficient protection against high-dose systemic infection. However, viral replication in solid non-lymphoid organs is not curtailed sufficiently fast to prevent significant virus-induced inflammation. Our results suggest that this is due to qualitative limitations of the primed CD8+ T cells.
Original language | English |
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Journal | European Journal of Immunology |
Volume | 33 |
Issue number | 7 |
Pages (from-to) | 1941-8 |
Number of pages | 7 |
ISSN | 0014-2980 |
DOIs | |
Publication status | Published - 2003 |
Bibliographical note
Keywords: Animals; Biolistics; CD8-Positive T-Lymphocytes; Cell Differentiation; Immunity, Cellular; Immunologic Memory; Mice; Vaccines, DNA
ID: 9701351