Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA

被引:190
作者
Ulmer, JB [1 ]
Fu, TM [1 ]
Deck, RR [1 ]
Friedman, A [1 ]
Guan, LM [1 ]
DeWitt, C [1 ]
Liu, X [1 ]
Wang, S [1 ]
Liu, MA [1 ]
Donnelly, JJ [1 ]
Caulfield, MJ [1 ]
机构
[1] Merck Res Labs, Dept Virus & Cell Biol, W Point, PA 19486 USA
关键词
D O I
10.1128/JVI.72.7.5648-5653.1998
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 effecters in protective immunity against influenza virus challenge conferred by NP DNA.
引用
收藏
页码:5648 / 5653
页数:6
相关论文
共 37 条
[21]   PROTECTION AGAINST MALARIA BY IMMUNIZATION WITH PLASMID DNA ENCODING CIRCUMSPOROZOITE PROTEIN [J].
SEDEGAH, M ;
HEDSTROM, R ;
HOBART, P ;
HOFFMAN, SL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (21) :9866-9870
[22]   GENETIC IMMUNIZATION IS A SIMPLE METHOD FOR ELICITING AN IMMUNE-RESPONSE [J].
TANG, DC ;
DEVIT, M ;
JOHNSTON, SA .
NATURE, 1992, 356 (6365) :152-154
[23]  
TAYLOR PM, 1986, IMMUNOLOGY, V58, P417
[24]   BETA(2)-MICROGLOBULIN-DEFICIENT MICE DEMONSTRATE CLASS-II MHC RESTRICTED ANTIVIRAL CD4(+) BUT NOT CD8(+) CTL AGAINST INFLUENZA-SENSITIZED AUTOLOGOUS SPLENOCYTES [J].
TAYLOR, SF ;
BENDER, BS .
IMMUNOLOGY LETTERS, 1995, 46 (1-2) :67-73
[25]  
TITE JP, 1990, IMMUNOLOGY, V71, P202
[26]  
TITE JP, 1990, IMMUNOLOGY, V70, P540
[27]   Immune CD4(+) T cells promote the clearance of influenza virus from major histocompatibility complex class II -/- respiratory epithelium [J].
Topham, DJ ;
Tripp, RA ;
Sarawar, SR ;
Sangster, MY ;
Doherty, PC .
JOURNAL OF VIROLOGY, 1996, 70 (02) :1288-1291
[28]   Clearance of an influenza A virus by CD4(+) T cells is inefficient in the absence of B cells [J].
Topham, DJ ;
Doherty, PC .
JOURNAL OF VIROLOGY, 1998, 72 (01) :882-885
[29]  
Ulmer J B, 1996, Adv Exp Med Biol, V397, P49
[30]   HETEROLOGOUS PROTECTION AGAINST INFLUENZA BY INJECTION OF DNA ENCODING A VIRAL PROTEIN [J].
ULMER, JB ;
DONNELLY, JJ ;
PARKER, SE ;
RHODES, GH ;
FELGNER, PL ;
DWARKI, VJ ;
GROMKOWSKI, SH ;
DECK, RR ;
DEWITT, CM ;
FRIEDMAN, A ;
HAWE, LA ;
LEANDER, KR ;
MARTINEZ, D ;
PERRY, HC ;
SHIVER, JW ;
MONTGOMERY, DL ;
LIU, MA .
SCIENCE, 1993, 259 (5102) :1745-1749