Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA.
DNA vaccination is an effective means of eliciting both humoral and cellular immunity, including cytotoxic T lymphocytes (CTL). Using an influenza virus model, we previously demonstrated that injection of DNA encoding influenza virus nucleoprotein (NP) induced major histocompatibility complex class I-restricted CTL and cross-strain protection from lethal virus challenge in mice (J. B. Ulmer et al., Science 259:1745-1749, 1993). In the present study, we have characterized in more detail the cellular immune responses induced by NP DNA, which included robust lymphoproliferation and Th1-type cytokine secretion (high levels of gamma interferon and interleukin-2 [IL-2], with little IL-4 or IL-10) in response to antigen-specific restimulation of splenocytes in vitro. These responses were mediated by CD4+ T cells, as shown by in vitro depletion of T-cell subsets. Taken together, these results indicate that immunization with NP DNA primes both cytolytic CD8+ T cells and cytokine-secreting CD4+ T cells. Further, we demonstrate by adoptive transfer and in vivo depletion of T-cell subsets that both of these types of T cells act as effectors in protective immunity against influenza virus challenge conferred by NP DNA.
Ulmer
J B
JB
Department of Virus and Cell Biology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Fu
T M
TM
Deck
R R
RR
Friedman
A
A
Guan
L
L
DeWitt
C
C
Liu
X
X
Wang
S
S
Liu
M A
MA
Donnelly
J J
JJ
Caulfield
M J
MJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007252:Influenza Vaccines / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics* / Q000276:immunology
D007252:Influenza Vaccines; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins