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.
Chen
Jian
J
1Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Wang
John
J
Li
Jun
J
Wu
Qi
Q
Chu Lim
Fei
F
Yang
Pingar
P
Hsu
Hui-Chen
HC
Curiel
David T
DT
Mountz
John D
JD
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