Effect of IL-12 on canine dendritic cell maturation following differentiation induced by granulocyte-macrophage CSF and IL-4

Sugiura, Kikuya; Wijewardana, Viskam; Fujimoto, Mai; Akazawa, Takashi; Yahata, Mana; Mito, Kai; Hatoya, Shingo; Inoue, Norimitsu; Inaba, Toshio

doi:10.1016/j.vetimm.2010.06.006

Cited by 11 publications

(10 citation statements)

References 22 publications

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“…CD83 is considered a relatively specific marker of mature DCs, correlated with the production of stable MHC-peptides required for potent T cell activation. In our study, we obtained PBMC-derived DCs by culturing blood monocytes in the presence of GM-CSF and IL-4 for 5 days [23,24], and we demonstrated that interaction of rhCnB with the DCs enhanced the expression of CD40, CD80, CD86, CD83, and HLA-DR. CnB also Fig. 3.…”

Section: Discussionmentioning

confidence: 84%

Calcineurin subunit B is an immunostimulatory protein and acts as a vaccine adjuvant inducing protective cellular and humoral responses against pneumococcal infection

Guo

et al. 2011

Immunology Letters

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Section: Discussionmentioning

confidence: 84%

Calcineurin subunit B is an immunostimulatory protein and acts as a vaccine adjuvant inducing protective cellular and humoral responses against pneumococcal infection

Guo

et al. 2011

Immunology Letters

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“…The affect of IL-12 on DC is less studied, but it has been observed that DC maturation/activation and IL-12 production may be tied events 19 . Recently this view has been refined by Sugiura et al reporting that IL-12 has a direct effect on DC maturation 20 . Here it is demonstrated that IL-12 paracrine/DC gene delivery induces those DC to stimulate a more robust CTL response in vitro.…”

Section: Introductionmentioning

confidence: 89%

AAV2/IL-12 gene delivery into dendritic cells (DC) enhances CTL stimulation above other IL-12 applications

et al. 2012

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Adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTL) holds significant promise in treating cancer and Th1 response cytokines are critical for their stimulation. Recently we reported that interleukin 7-(IL-7) and interferongamma-(IFNγ) autocrine/T cell gene delivery resulted in superior ex vivo CTL stimulation over paracrine/DC delivery. IL-12 is yet another important Th1 cytokine which affects both DC and T cells. Here, using adeno-associated virus Type 2 (AAV2) gene delivery, IL-12-paracrine/DC gene delivery gave significantly superior stimulation of carcinoembryonic antigen (CEA)-specific CTL killing over that induced by autocrine gene delivery (or exogenous IL-12 addition). This is surprising as both AAV2/IL-12-treated T cells and DC secreted approximately the same level of IL-12. Paracrine IL-12 gene delivery also resulted in highest IL-12/IL-10 secretion ratio by DC and highest CD40, CD80, CD83 and CD86 expression. Moreover, AAV2/IL-12-DC stimulated the highest T-cell IFNγ production, highest T cell proliferation, highest CD69+/CD8+ levels, and lowest level of CD25+/CD4+ Treg. These data strongly suggest that the primary activity of IL-12 during CTL generation is upon the DC. These data are also consistent with there being novel activity for IL-12 within the DC itself, not involving its surface receptor; an “intracrine” activity. Given the plethora of IL-12 studies, these data also suggest that this gene delivery comparison approach could be useful for uncovering new cytokine activities and mechanism(s) of action gone unrecognized by conventional immunologic assays. Finally, these data further suggest AAV2/IL-12 intracrine gene delivery into DC may have utility in immunotherapy protocols involving antigen-specific CTL.

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“…Flow cytometry : Flow cytometry (FCM) was performed as described previously [ 17 , 20 ]. Cells harvested from the cultures were stained with the following monoclonal antibodies (mAbs): FITC-conjugated mouse anti-human CD1a mAb (clone NA1/34-HLK, Serotec, Oxford, U.K.), rat anti-canine MHC class II mAb (clone YKIX.334.2, Serotec), PE-Cy5-conjugated mouse anti-human CD14 mAb (clone TÜK4, Serotec), biotin conjugated rat anti-mouse CD80 mAb (clone 1G10, Becton Dickinson, Franklin Lakes, NJ, U.S.A.) and mouse anti-human CD86 mAb (clone FUN-1, Becton Dickinson).…”

Section: Methodsmentioning

confidence: 99%

“…DCs exist in both immature and mature stages. We also found a significant increase in expression of immune-stimulatory molecules during maturation of the dog DCs [ 17 , 20 ]. In contrast to mature DCs, immature DCs were reported to induce tolerance [ 10 ].…”

mentioning

confidence: 99%

Effect of ovarian hormones on maturation of dendritic cells from peripheral blood monocytes in dogs

Wijewardana

Sugiura

Wijesekera

et al. 2015

The Journal of Veterinary Medical Science

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Previously, we reported that ovarian hormones affect the immune response against E. coli isolated from the dogs affected with pyometra. In order to investigate mechanisms underlying the immune modulation, we examined the effects of ovarian hormones on the generation of dendritic cells (DCs), the most potent antigen presenting cell. DCs were differentiated from peripheral blood monocytes (PBMOs) using a cytokine cocktail. Both estrogen receptor and progesterone receptors were expressed by the PBMOs and immature DCs. When various ovarian hormones were added to the culture for the DC differentiation, progesterone significantly decreased the expression of DC maturation markers, such as CD1a, CD80 and CD86, on mature DCs. Conversely, the addition of estrogen to the cultures increased the expression of CD86, but not other maturation makers. Furthermore, DCs differentiated in the presence of progesterone did not stimulate allogeneic mononuclear cells in PB. Taken together, these results indicate that progesterone diminishes the maturation of DCs, leading to decreased immune responses against invading pathogens.

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Effect of IL-12 on canine dendritic cell maturation following differentiation induced by granulocyte-macrophage CSF and IL-4

Cited by 11 publications

References 22 publications

Calcineurin subunit B is an immunostimulatory protein and acts as a vaccine adjuvant inducing protective cellular and humoral responses against pneumococcal infection

Calcineurin subunit B is an immunostimulatory protein and acts as a vaccine adjuvant inducing protective cellular and humoral responses against pneumococcal infection

AAV2/IL-12 gene delivery into dendritic cells (DC) enhances CTL stimulation above other IL-12 applications

Effect of ovarian hormones on maturation of dendritic cells from peripheral blood monocytes in dogs

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