FUNCTIONAL ACTIVITY OF IFNα- AND IL-4-INDUCED HUMAN DENDRITIC CELLS: A COMPARATIVE STUDY
https://doi.org/10.15789/1563-0625-2014-1-43-52
Abstract
We have performed a comparative analysis of allostimulatory, Th1/Th2-stimulatory and
tolerogenic activities of dendritic cells (DCs) derived from healthy donors (n = 52). The DCs were generated
in vitro with IFN-alpha (IFN-DCs) or IL-4 (IL-4-DCs). It was shown that IL-4-DCs and IFN-DCs did
not differ in their key functional characteristics, i.e., in their ability to stimulate proliferation of T-cells in
response to alloantigens, and to induce generation of T-regulatory cells in mixed leukocyte culture. IFN- and
IL-4-induced DCs possess similar ability of boosting T cells to produce Th1/proinflammatory (IFNγ, IL-2,
IL-1β, TNFα, IL-12, IL-17) and Th2/antiinflammatory cytokines (IL-4, IL-6, IL-10, IL-13), growth factors
(G-CSF, GM-CSF, IL-7) and chemokines (IL-8, MIP-1β). Nevertheless, IFN-DCs have more pronounced
stimulatory effect upon Th1 and Th2 cells, thus manifesting as a significantly higher IFNγ, IL-5 and MIP-1β
production. IFN-DCs were characterized by more prominent ability to activate Th1-cells, and by moderate
Th2-stimulatory activity, which is absent in IL-4-DCs. These data strongly suggest that IFN-DCs may present
a quite promising cellular tool for development of therapeutic vaccines aiming to induce/enhance the immune
response.
About the Authors
O. Yu. Leplina
Research Institute of Clinical Immunology, Russian Academy of Medical Sciences, Siberian Branch, Novosibirsk
Russian Federation
PhD, MD (Medicine), Senior Researcher Fellow
Russian Federation
PhD, MD (Medicine), Senior Researcher Fellow
M. A. Tikhonova
Research Institute of Clinical Immunology, Russian Academy of Medical Sciences, Siberian Branch, Novosibirsk
Russian Federation
PhD (Biology), Senior Researcher
Russian Federation
PhD (Biology), Senior Researcher
T. V. Tyrinova
Research Institute of Clinical Immunology, Russian Academy of Medical Sciences, Siberian Branch, Novosibirsk
Russian Federation
PhD (Biology), Research Associate
Russian Federation
PhD (Biology), Research Associate
E. A. Alyamkina
Institute of Cytology and Genetics, Russian Academy of Sciences, Siberian Branch, Novosibirsk
Russian Federation
PhD (Biology)
Russian Federation
PhD (Biology)
S. S. Bogachev
Institute of Cytology and Genetics, Russian Academy of Sciences, Siberian Branch, Novosibirsk
Russian Federation
PhD, MD (Biology), Head of the Laboratory
Russian Federation
PhD, MD (Biology), Head of the Laboratory
A. A, Ostanin
Research Institute of Clinical Immunology, Russian Academy of Medical Sciences, Siberian Branch
Russian Federation
Russian Federation
PhD, MD (Medicine), Professor, Chief Research
Associate
E. R. Chernykh
Research Institute of Clinical Immunology, Russian Academy of Medical Sciences, Siberian Branch
Russian Federation
Russian Federation
PhD, MD (Medicine), Professor, Corresponding
member, Russian Academy of Medical Sciences, Head of
Laboratory
References
1. Леплина О.Ю., Ступак В.В., Козлов Ю.П., Пендюрин И.В., Никонов С.Д., Тихонова М.А., Сычева Н.В., Останин А.А., Черных Е.Р. Применение интерферон-α-индуцированных дендритных клеток при лечении больных со злокачественными глиомами головного мозга // Клеточные технологии в биологии и медицине. – 2007. – № 2. – С. 92-98. Leplina O.Yu., Stupak V.V., Kozlov Yu.P., Pendyurin I.V., Nikonov S.D., Tikhonova M.A., Sycheva N.V., Ostanin A.A., Chernykh E.R. Primenenie interferon-α-indutsirovannykh dendritnykh kletok pri lechenii bol`nykh so zlokachestvennymi gliomami golovnogo mozga [Use of Interferon-α-Induced Dendritic Cells in the Therapy of Patients with Malignant Brain Gliomas]. Kletochnye tekhnologii v biologii i meditsine – Cell Technologies in Biology and Medicine, 2007, no. 2, pp. 92-98.
2. Леплина О.Ю., Желтова О.И., Борисова А.Е., Старостина Н.М., Останин А.А. Вакцины на основе дендритных клеток в лечении герпетической инфекции // Вестник Уральской медицинской академической науки. – 2011. – Т. 35, № 2/2. – С. 38-39. Leplina O.Yu., Zheltova O.I., Borisova A.E., Starostina N.M., Ostanin A.A., Vaktsiny na osnove dendritnykh kletok v lechenii gerpeticheskoy infektsii [Dendritic cells vaccines in the trearment of herpeticinfections]. Vestnik Ural`skoy meditsinskoy akademicheskoy nauki – Journal of the Ural Academic Science, 2011, vol. 35, no. 2/2, pp. 38-39.
3. Леплина О.Ю., Тихонова М.А., Тыринова Т.В., Алямкина Е.А., Долгова Е.В, Богачев С.С. Останин А.А., Черных, Е.Р. Сравнительная характеристика фенотипа и цитокин-секреторной активности дендритных клеток человека, генерированных in vitro в присутствии IFN-альфа и IL-4 // Иммунология. – 2012. – Т. 33, № 2. – С. 60-65. Leplina O.Yu., Tikhonova M.A., Tyrinova T.V., Alyamkina E.A.,. Dolgova E.V, Bogachev S.S. Ostanin A.A., Chernykh, E.R. Sravnitel`naya kharakteristika fenotipa i tsitokin-sekretornoy aktivnosti dendritnykh kletok cheloveka, generirovannykh in vitro v prisutstvii IFN-al`fa i IL-4 [Comparative characteristic of phenotype and cytokine-secretory activity of human dendritic cells generated in vitro with IFN-alpha and IL- 4]. Immunologiya – Immunology, 2012, vol. 33, no. 2, pp. 60-65.
4. Черных Е.Р., Леплина О.Ю., Ступак В.В., Пендюрин И.В., Никонов С.Д., Тихонова М.А., Останин А.А. Клеточные технологии в лечении злокачественных глиом головного мозга // «Клеточные технологии. Теоретические и прикладные аспекты», Сборник трудов под ред. Козлова В.А., Сенникова С.В., Черных Е.Р., Останина А.А. – Новосибирск: Наука, 2009. – С. 240-276. Chernykh E.R., Leplina O.Yu., Stupak V.V., Pendyurin I.V., Nikonov S.D., Tikhonova M.A., Ostanin A.A. Kletochnye tekhnologii v lechenii zlokachestvennykh gliom golovnogo mozga .“Kletochnye tekhnologii. Teoreticheskie i prikladnye aspekty”, Sbornik trudov pod red. Kozlova V.A., Sennikova S.V., Chernykh E.R., Ostanina A.A. [Cell technologies in malignant brain gliomas treatment. Proceedings. Eds.: V.A. Kozlov, S.V. Sennikov, E.R. Chernykh, A.A. Ostanina]. Novosibirsk: Science, 2009, pp. 240-276
5. Alyamkina E.A., Leplina O.Y., Ostanin A.A., Chernykh E.R., Nikolin V.P., Popova N.A., Proskurina A.S., Gvozdeva T.S., Dolgova E.V., Orishchenko K.E., Rogachev V.A., Sidorov S.V., Varaksin N.A., Ryabicheva T.G., Bogachev S.S., Shurdov M.A. Effects of human exogenous DNA on production of perforincontaining CD8+ cytotoxic lymphocytes in laboratory setting and clinical practice. Cell Immunol., 2012, vol. 276, no. 1-2, pp. 59-66.
6. Banchereau J., Steinman. R.M. Dendritic cells and the control of immunity. Nature, 1998, vol. 392, pp. 245-252.
7. Belardelli F., Gresser I. The neglected role of type I interferon in the T-cell response: implications for its clinical use. Immunol. Today, 1996, vol. 17, pp. 369-375.
8. Belkaid Y., Oldenhove G. Tuning microenvironments: induction of regulatory T cells by dendritic cells Immunity, 2008, vol. 29, pp. 362-371.
9. Billerbeck E., Blum H.E., Thimme R. Parallel expansion of human virus-specific FoxP3 effector memory and de novo-generated FoxP3+ regulatory CD8+ T cells upon antigen recognition in vitro. Immunol., 2007, vol. 179, pp. 1039-1048.
10. Cicinnati V.R., Kang J., Hou J., Lindemann M., Koop K., T ting T., Gerken G., Beckebaum S. Interferonalpha differentially affects homeostasis of human plasmacytoid and myeloid dendritic cells. J. Interferon Cytokine Res., 2009, vol. 29, pp. 145-160.
11. Dieckmann D., Bruett C.H., Ploettner H., Lutz M.B., Schuler G. Human CD4+CD25+ regulatory, contact-dependent T cells induce interleukin 10-producing, contact-independent type 1-like regulatory T cells. J. Exp. Med., 2002, vol. 196, no. 2, pp. 247-253.
12. Della Bella S., Nicola S., Riva A., Biasin M., Clerici M., Villa M.L. Functional repertoire of dendritic cells generated in granulocyte macrophage-colony stimulating factor and interferon-α. J. Leuk. Biol., 2004, vol. 75, pp. 106-116.
13. Leplina O.Yu., Tyrinova T.V., Tikhonova M.A., Shevela E.Ya., Stupak V.V., Mishinov S.V., Pendyurin I., Sadovoy M., Ostanin A.A., Chernykh E.R. Direct antitumor activity of interferon-induced dendritic cells of healthy donors and patients with primary brain tumors. In book: “Glioma – exploring it’s biology and practical relevance” edited by Anirban Ghosh, 2011, pp. 325-342.
14. Lutz M.B., Schuler G. Immature, semi-mature, and fully mature dendritic cells: Which signals induce tolerance or immunity? Trends Immunol, 2002, vol. 23, pp. 445-449.
15. Mohty M., Vialle-Castellano A., Nunes J.A., Isnardon D., Olive D., Gaugler B. IFN-a skews monocyte differentiation into Toll-like receptor 7-expressing dendritic cells with potent functional activities. J. Immunol.,2003, vol. 171, pp. 3385-3393.
16. Moser M., Murphy K.M. Dendritic cell regulation of Th1-Th2 development. Nat. Immunol., 2000, vol. 1, pp. 199-205.
17. Parlato S., Santini S., Lapenta C., Di Pucchio T., Logozzi M., Spada M., Giammarioly A., Malorni W., Fais S., Bellardelli F. Expression of CCR-7, MIP-3b, and Th1 chemokines in type I IFN-induced monocytederived dendritic cells – importance for the rapid acquisition of potent migratory and functional activities. Blood, 2001, vol. 98, pp. 3022-3029.
18. Santini S., Lapenta C., Logozzi M., Parlato S., Spada M., Di Pucchio T., Bellardelli F. Type I Interferon as a powerful adjuvant for monocyte-derived dendritic cells development and activity in vitro and in HU-PBLSCID mice. J. Exp. Med., 2000, vol. 191, pp. 1777-1788.
19. Santini S., Pucchini T., Lapenta C., Parlato S., Logozzi M., Belardelli F. A new type 1 IFN-mediated pathway for the rapid differentiation of monocytes into highly active dendritic cells. Stem cells, 2003, vol. 21, pp. 357-362.
20. Santini S., Lapenta C, Santodonato L, D’Agostino G, Belardelli F, Ferrantini M. IFNα in the generation of dendritic cells for cancer immunotherapy. Handb. Exp. Pharmacol., 2009, vol. 188, pp. 295-317.
21. Santini S., Lapenta C., Donati S., Spadaro F., Belardelli F., Ferrantini M. Interferon-a-conditioned human monocytes combine Th1-orienting attitude with the induction of autologous Th17 responses: role of IL-23 and IL- 12. PLoS ONE, 2011, vol. 6, e 17364, doi 10.1371.
22. Thurner B., Roder C., Dieckmann D., Heuer M., Kruse M., Glaser A., Keikavoussi P., Kampgen E., Bender A., Schuler G. Generation of large numbers of fully mature and stable dendritic cells from leukapheresis products for clinical applications. J. Immunol. Meth., 1999, vol. 223, pp. 1-15.
Review
For citations:
Leplina O.Yu., Tikhonova M.A., Tyrinova T.V., Alyamkina E.A., Bogachev S.S., Ostanin A.A., Chernykh E.R. FUNCTIONAL ACTIVITY OF IFNα- AND IL-4-INDUCED HUMAN DENDRITIC CELLS: A COMPARATIVE STUDY. Medical Immunology (Russia). 2014;16(1):43-52. (In Russ.) https://doi.org/10.15789/1563-0625-2014-1-43-52
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