Differential regulation of antigen-specific CD8(+) T cell responses by IL-12p40 in a dose-dependent manner
SCIE
SCOPUS
- Title
- Differential regulation of antigen-specific CD8(+) T cell responses by IL-12p40 in a dose-dependent manner
- Authors
- Kim, DJ; Youn, JI; Seo, SH; Jin, HT; Sung, YC
- Date Issued
- 2008-06-01
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Abstract
- IL-12p40 is a natural antagonist which inhibits IL-12- and IL-23-mediated biological activity by blocking the binding of IL-12/23 to their receptors. Recently, IL-12p40 was also shown to have immune-enhancing activity through the activation of macrophages or dendritic cells. In this study, we investigated the effects of IL-12p40 as a genetic adjuvant on immune modulation using recombinant adenoviruses expressing IL-12p40 (rAd/IL-12p40) and OVA (rAd/OVA). Coimmunization of rAd/IL-12p40 at a low dose (1 x 10(4) PFU) with rAd/OVA resulted in OVA-specific immune enhancement, while a high dose of rAd/IL-12p40 (1 x 10(8) PFU) caused significant suppression of CD8(+) T cell responses. In addition, the enhancement and suppression of OVA-specific CD8(+) T cell responses correlated with antitumor activity against E.G7-OVA tumor challenge, which subsequently affected the survival rate. Moreover, the differential CD8(+) T cell response by IL-12p40 was still observed in IL-12R beta 2 knockout (IL-12R beta 2KO), but not in IL-12R beta 1 knockout (IL-12R beta 1KO) mice, indicating that IL-12p40 is a cytokine which can modulate Ag-specific T cell responses depending on IL-12R beta 1. Our findings provide a novel insight on the physiological role of IL-12p40, which can be informative in the design of vaccine strategies and therapeutic regimens.
- Keywords
- NITRIC-OXIDE SYNTHASE; NATURAL-KILLER-CELLS; NF-KAPPA-B; P40 HOMODIMER; STIMULATORY FACTOR; TYROSINE PHOSPHORYLATION; HETERODIMERIC CYTOKINE; INTERLEUKIN-12 P40; SIGNAL TRANSDUCER; HUMAN-LYMPHOCYTES
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/22656
- DOI
- 10.4049/jimmunol.180.11.7167
- ISSN
- 0022-1767
- Article Type
- Article
- Citation
- JOURNAL OF IMMUNOLOGY, vol. 180, no. 11, page. 7167 - 7174, 2008-06-01
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