Incomplete effector/memory differentiation of antigen-primed CD8+ T cells in gene gun DNA-vaccinated mice.
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.
Bartholdy
Christina
C
Institute of Medical Microbiology and Immunology, The Panum Institute, University of Copenhagen, 3C Blegdamsvej, DK-2200 N Copenhagen, Denmark.
Stryhn
Anette
A
Hansen
Nils Jacob Vest
NJ
Buus
Søren
S
Thomsen
Allan Randrup
AR
D000818:Animals; D019470:Biolistics; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology*; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D051379:Mice; D019444:Vaccines, DNA / Q000494:pharmacology*
D019444:Vaccines, DNA