Enhancement of cytotoxic T-lymphocyte response in aged mice by a novel treatment with recombinant AdIL-12 and wild-type adenovirus in rapid succession.
A decrease in the expression of Th1 cytokines has been associated with age-related decrease in cytotoxic T-lymphocyte (CTL) function. We utilized an E1-deleted adenovirus (Ad) vector to deliver the murine interleukin-12 (IL-12) gene in order to enhance the antivirus CTL response. Wild-type (WT) Ad was administered 3 days after AdIL-12 treatment, when IL-12 production was at its peak and the anti-Ad antibody response had not yet begun to develop. Before receiving AdIL-12 treatment, aged (18 month old) mice exhibited a 58% decrease in the number of virus-specific CTLs, and a 30% decrease in in vivo CTL activity as compared to young (2 month old) mice. After AdIL-12 treatment, aged mice displayed a greater increase in IL-12 expression and endogenous production of interferon-gamma than observed in young mice. When infected with WT Ad, these AdIL-12-treated aged mice exhibited an increased in vivo CTL response and an in vitro proliferative response that was similar to those in young mice. The frequencies of occurrence of D(b)-E1Bp(+)CD8(+) T cells in the spleen, liver, and lung in aged mice were higher than the corresponding values in young mice. These results indicate that IL-12 treatment significantly promotes the virus-specific CTL response in aged mice and, more importantly, specifically targets the virally infected organs, such as the liver and lung, promoting enhanced CTL activity against the virus.
1Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Jian
J
Chen
John
J
Wang
Jun
J
Li
Qi
Q
Wu
Fei
F
Chu Lim
Pingar
P
Yang
Hui-Chen
HC
Hsu
David T
DT
Curiel
John D
JD
Mountz
D000256:Adenoviridae / Q000235:genetics*; D000367:Age Factors; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D005838:Genotype; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D018664:Interleukin-12 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D011993:Recombinant Fusion Proteins; D018664:Interleukin-12; D007371:Interferon-gamma