2008
DOI: 10.1038/mt.2008.121
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Enhancement of Cytotoxic T-lymphocyte Response in Aged Mice by a Novel Treatment with Recombinant AdIL-12 and Wild-type Adenovirus in Rapid Succession

Abstract: 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 exhi… Show more

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Cited by 14 publications
(4 citation statements)
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“…Several regenerative approaches have been explored with the aim of restoring thymopoiesis in animal models of aging. 12,[29][30][31][32][33] None to date have been entirely satisfactory. Keratinocyte growth factor, 34,35 growth hormone 36 or ghrelin 29 reorganize thymic architecture by acting on thymic epithelial cells with only modest effect on lymphoid progenitors.…”
Section: Discussionmentioning
confidence: 98%
See 1 more Smart Citation
“…Several regenerative approaches have been explored with the aim of restoring thymopoiesis in animal models of aging. 12,[29][30][31][32][33] None to date have been entirely satisfactory. Keratinocyte growth factor, 34,35 growth hormone 36 or ghrelin 29 reorganize thymic architecture by acting on thymic epithelial cells with only modest effect on lymphoid progenitors.…”
Section: Discussionmentioning
confidence: 98%
“…Several regenerative approaches have been explored with the aim of restoring thymopoiesis in animal models of aging 12 , 29 , 30 , 31 , 32 , 33 . None to date have been entirely satisfactory.…”
Section: Discussionmentioning
confidence: 99%
“…Although IL-12 levels are not decreased in aging wildtype animals, thymic involution was accelerated in aging IL-12b-/- mice, and in vitro stimulation of thymocytes with IL-7 or IL-2 in combination with IL-12 led to synergistic enhancement of proliferation [66]. Additionally, Chen et al recently demonstrated that adenoviral administration of IL-12 (AdIL-12) to aging mice followed by wildtype adenoviral treatment resulted in enhanced cytotoxic lymphocyte (CTL) responses measured in vitro and in vivo [67]. The aging mice (18 months old) treated with AdIL-12 secreted greater levels of IFNγ, showed comparable T cell proliferative responses to those in young mice, and demonstrated efficient antigen-specific killing in vitro.…”
Section: Interleukin (Il)-7 Il-12 Il-15mentioning
confidence: 99%
“…These include IGF-1, which promotes TEC expansion and enhances reconstitution following HSCT (7173); IL-15, which predominantly promotes proliferation of circulating NK and T cells (74, 75); and IL-12, which stimulates thymic expression of IL-7 and enhances hematopoietic engraftment after transplant (7678), although IL-12 and IL-15 have also been recently found to also act on regulatory lymphoid-tissue inducer cells and NK cells (79, 80). …”
Section: Toolkit For Immune Regenerationmentioning
confidence: 99%