Noradrenaline modulates CD4+ T cell priming in rat experimental autoimmune encephalomyelitis: a role for the α1-adrenoceptor

  • Ivan Pilipović
  • Ivana Vujnović
  • Zorica Stojić-Vukanić
  • Raisa Petrović
  • Duško Kosec
  • Mirjana Nacka-Aleksić
  • Nebojša Jasnić
  • Gordana LeposavićEmail author
Original Article


Pharmacological blockade of α1-adrenoceptor is shown to influence development of experimental autoimmune encephalomyelitis (EAE), an IL-17-producing CD4+TCR+ (Th17) cell-mediated disease mimicking multiple sclerosis. Considering significance of CD4+ cell priming for the clinical outcome of EAE, the study examined α1-adrenoceptor-mediated influence of catecholamines, particularly those derived from draining lymph node (dLN) cells (as catecholamine supply from nerve fibers decreases with the initiation of autoimmune diseases) for CD4+ cell priming. The results confirmed diminishing effect of immunization on nerve fiber-derived noradrenaline supply and showed that antigen presenting and CD4+ cells synthesize catecholamines, while antigen presenting cells and only CD4+CD25+Foxp3+ regulatory T cells (Tregs) express α1-adrenoceptor. The analysis of influence of α1-adrenoceptor antagonist prazosin on the myelin basic protein (MBP)-stimulated CD4+ lymphocytes in dLN cell culture showed their diminished proliferation in the presence of prazosin. This was consistent with prazosin enhancing effect on Treg frequency and their Foxp3 expression in these cultures. The latter was associated with upregulation of TGF-β expression. Additionally, prazosin decreased antigen presenting cell activation and affected their cytokine profile by diminishing the frequency of cells that produce Th17 polarizing cytokines (IL-1β and IL-23) and increasing that of IL-10-producing cells. Consistently, the frequency of all IL-17A+ cells and those co-expressing GM-CSF within CD4+ lymphocytes was decreased in prazosin-supplemented MBP-stimulated dLN cell cultures. Collectively, the results indicated that dLN cell-derived catecholamines may influence EAE development by modulating interactions between distinct subtypes of CD4+ T cells and antigen presenting cells through α1-adrenoceptor and consequently CD4+ T cell priming.


Noradrenaline α1-Adrenoceptor EAE Tregs Th17 CD4+ lymphocyte proliferation 


Author contributions

GL, ZSV, IP, and IV designed the study. GL, ZSV, and IV wrote the manuscript. GL, ZSV, IP, IV, RP, DK, MNA, and NJ participated in experiments, data analysis and/or interpretation, and critically reviewed and approved the manuscript.


This work was supported by the Ministry of Education, Science, and Technological Development of the Republic of Serbia (grant number 175050).

Compliance with ethical standards

All experimental procedures and animal care were performed in accordance with the Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes (revising Directive 86/609/EEC) and approved by the Animal Care and Use Committee of the Faculty of Pharmacy (permit number 6/12). The experiments complied with the ARRIVE guidelines for reporting animal research.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

12026_2019_9082_MOESM1_ESM.tif (347 kb)
Online Resource 1 Arterenol failed to increase CD4+ lymphocyte proliferation in dLN cell cultures from EAE rats in the presence of α1-adrenoceptor blocker. (a) Flow cytometry histogram indicates the gating strategy for proliferating cells (cells in S+G2/M phases of the cell cycle), as determined using 7-AAD (Materials and methods section), within CD4+ lymphocytes (gated as shown in right flow cytometry dot plot), following (left flow cytometry dot plot) the elimination of cellular debris and doublets using pulse processing. (b) Bar graph indicates the frequency of proliferating cells among CD4+ lymphocytes from 72 h dLN cell cultures of female and male rats immunized for EAE (EAE rats) following stimulation with MBP in the absence or in the presence of 10-6 M of arterenol (Art), with or without 10-5 M of prazosin (Pz) (Materials and methods section). The data are shown as mean±SEM (n=6). * p<0.05; ** p<0.01; *** p<0.001; # p<0.05; ### p<0.001. # vs Female. a vs unstimulated; b vs MBP; c vs MBP+Art; d vs MBP+Pz (TIF 347 kb)
12026_2019_9082_Fig10_ESM.png (45 kb)
High Resolution Image (PNG 45 kb)
12026_2019_9082_MOESM3_ESM.tif (371 kb)
Online Resource 2 Prazosin did not influence the proliferation of MACS-separated conventional dLN CD4+CD25- cells. Representative flow cytometry contour plot panel indicates the expression of Ki-67 proliferation marker in MACS-separated conventional male EAE rat dLN CD4+CD25- lymphocytes following 72 h in vitro stimulation with anti-CD3/CD28 mAbs in the absence or in the presence of prazosin, and in the absence of cognate stimuli (Control) (Materials and methods section). Fluorescence minus one (FMO) control incubated with isotype-matched control instead of anti-Ki-67 antibody (-Ki-67 Ab) was used to set the cut-off boundary for Ki-67 expression analysis in MACS-sorted CD4+CD25- cells from cell cultures. Statistical significance of differences was assessed using one-way ANOVA followed by Tukey test for post-hoc comparisons. $$ p<0.01. $ vs Control (TIF 371 kb)
12026_2019_9082_Fig11_ESM.png (75 kb)
High Resolution Image (PNG 75 kb)


  1. 1.
    Constantinescu CS, Farooqi N, O’brien K, Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol. 2011;164:1079–106.CrossRefGoogle Scholar
  2. 2.
    Lassmann H, Bradl M. Multiple sclerosis: experimental models and reality. Acta Neuropathol. 2017;133:223–44.CrossRefGoogle Scholar
  3. 3.
    Codarri L, Gyülvészi G, Tosevski V, Hesske L, Fontana A, Magnenat L, et al. RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol. 2011;12:560–7.CrossRefGoogle Scholar
  4. 4.
    El-Behi M, Ciric B, Dai H, Yan Y, Cullimore M, Safavi F, et al. The encephalitogenicity of T(H) 17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol. 2011;12:568–75.CrossRefGoogle Scholar
  5. 5.
    Lukic ML, Saleh AM, Mensah-Brown E, Camasamudram V, Shahin A. Strain differences in susceptibility to experimental allergic encephalomyelitis in rats: molecular regulation at the level of the target tissue. Frontiers in autoimmunity: fundamental aspects and clinical perspectives, NATO Science Series I. Amsterdam: Ios Press, 2003, pp. 29–44.Google Scholar
  6. 6.
    Danke NA, Koelle DM, Yee C, Beheray S, Kwok WW. Autoreactive T cells in healthy individuals. J Immunol. 2004;172:5967–72.CrossRefGoogle Scholar
  7. 7.
    Schiffmann S, Weigert A, Männich J, Eberle M, Birod K, Häussler A, et al. PGE2/EP4 signaling in peripheral immune cells promotes development of experimental autoimmune encephalomyelitis. Biochem Pharmacol. 2014;87:625–35.CrossRefGoogle Scholar
  8. 8.
    Miller LE, Jüsten HP, Schölmerich J, Straub RH. The loss of sympathetic nerve fibers in the synovial tissue of patients with rheumatoid arthritis is accompanied by increased norepinephrine release from synovial macrophages. FASEB J. 2000;14:2097–107.CrossRefGoogle Scholar
  9. 9.
    Cosentino M, Zaffaroni M, Marino F, Bombelli R, Ferrari M, Rasini E, et al. Catecholamine production and tyrosine hydroxylase expression in peripheral blood mononuclear cells from multiple sclerosis patients: effect of cell stimulation and possible relevance for activation-induced apoptosis. J Neuroimmunol. 2002;133:233–40.CrossRefGoogle Scholar
  10. 10.
    Capellino S, Weber K, Gelder M, Härle P, Straub RH. First appearance and location of catecholaminergic cells during experimental arthritis and elimination by chemical sympathectomy. Arthritis Rheumatol. 2012;64:1110–8.CrossRefGoogle Scholar
  11. 11.
    Huang HW, Fang XX, Wang XQ, Peng YP, Qiu YH. Regulation of differentiation and function of helper T cells by lymphocyte-derived catecholamines via α1-and β2-adrenoceptors. Neuroimmunomodulation. 2015;22:138–51.CrossRefGoogle Scholar
  12. 12.
    Huang HW, Zuo C, Chen X, Peng YP, Qiu YH. Effect of tyrosine hydroxylase overexpression in lymphocytes on the differentiation and function of T helper cells. Int J Mol Med. 2016;38:635–42.CrossRefGoogle Scholar
  13. 13.
    Brosnan CF, Goldmuntz EA, Cammer W, Factor SM, Bloom BR, Norton WT. Prazosin, an alpha 1-adrenergic receptor antagonist, suppresses experimental autoimmune encephalomyelitis in the Lewis rat. Proc Natl Acad Sci U S A. 1985;82:5915–9.CrossRefGoogle Scholar
  14. 14.
    Chelmicka-Schorr E, Checinski M, Arnason BG. Chemical sympathectomy augments the severity of experimental allergic encephalomyelitis. J Neuroimmunol. 1988;17:347–50.CrossRefGoogle Scholar
  15. 15.
    Dimitrijević M, Rauški A, Radojević K, Kosec D, Stanojević S, Pilipović I, et al. β-Adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats. Eur J Pharmacol. 2007;577:170–82.CrossRefGoogle Scholar
  16. 16.
    Vujnović I, Pilipović I, Jasnić N, Petrović R, Blagojević V, Arsenović-Ranin N, et al. Noradrenaline through β-adrenoceptor contributes to sexual dimorphism in primary CD4+ T-cell response in DA rat EAE model? Cell Immunol. 2019;336:48–57.CrossRefGoogle Scholar
  17. 17.
    Brosnan CF, Sacks HJ, Goldschmidt RC, Goldmuntz EA, Norton WT. Prazosin treatment during the effector stage of disease suppresses experimental autoimmune encephalomyelitis in the Lewis rat. J Immunol. 1986;137:3451–6.Google Scholar
  18. 18.
    Goldmuntz EA, Brosnan CF, Norton WT. Prazosin treatment suppresses increased vascular permeability in both acute and passively transferred experimental autoimmune encephalomyelitis in the Lewis rat. J Immunol. 1986;137:3444–50.Google Scholar
  19. 19.
    White SR, Black PC, Samathanam GK, Paros KC. Prazosin suppresses development of axonal damage in rats inoculated for experimental allergic encephalomyelitis. J Neuroimmunol. 1992;39:211–8.CrossRefGoogle Scholar
  20. 20.
    Nacka-Aleksić M, Djikić J, Pilipović I, Stojić-Vukanić Z, Kosec D, Bufan B, et al. Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: sexual dimorphism and diergism at the spinal cord level. Brain Behav Immun. 2015;49:101–18.CrossRefGoogle Scholar
  21. 21.
    Priyanka HP, ThyagaRajan S. Selective modulation of lymphoproliferation and cytokine production via intracellular signaling targets by α1- and α2-adrenoceptors and estrogen in splenocytes. Int Immunopharmacol. 2013;17:774–84.CrossRefGoogle Scholar
  22. 22.
    Padro CJ, Sanders VM. Neuroendocrine regulation of inflammation. Semin Immunol. 2014;26:357–68.CrossRefGoogle Scholar
  23. 23.
    Alvarez DF, Helm K, DeGregori J, Roederer M, Majka S. Publishing flow cytometry data. Am J Physiol Lung Cell Mol Physiol. 2010;298:L127–30.CrossRefGoogle Scholar
  24. 24.
    Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. The sympathetic nerve – an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. 2000;52:595–638.Google Scholar
  25. 25.
    Damsker JM, Hansen AM, Caspi RR. Th1 and Th17 cells. Ann N Y Acad Sci. 2010;1183:211–21.CrossRefGoogle Scholar
  26. 26.
    Flatmark T, Stevens RC. Structural insight into the aromatic amino acid hydroxylases and their disease-related mutant forms. Chem Rev. 1999;99:2137–60.CrossRefGoogle Scholar
  27. 27.
    Qiu YH, Cheng C, Dai L, Peng YP. Effect of endogenous catecholamines in lymphocytes on lymphocyte function. J Neuroimmunol. 2005;167:45–52.CrossRefGoogle Scholar
  28. 28.
    Jiang JL, Peng YP, Qiu YH, Wang JJ. Effect of the endogenous catecholamines synthesized by lymphocytes on T cell proliferation. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2009;25:81–5.Google Scholar
  29. 29.
    Pilipović I, Vujnović I, Arsenović-Ranin N, Dimitrijević M, Kosec D, Stojić-Vukanić Z, et al. Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats. J Neuroimmunol. 2016;297:103–16.CrossRefGoogle Scholar
  30. 30.
    Hadden JW, Hadden EM, Middleton E Jr. Lymphocyte blast transformation: I. Demonstration of adrenergic receptors in human peripheral lymphocytes. Cell Immunol. 1970;1:583–95.CrossRefGoogle Scholar
  31. 31.
    Hiramoto T, Ihara Y, Watanabe Y. α-1 adrenergic receptors stimulation induces the proliferation of neural progenitor cells in vitro. Neurosci Lett. 2006;408:25–8.CrossRefGoogle Scholar
  32. 32.
    Liou SF, Lin HH, Liang JC, Chen J, Yeh JL. Inhibition of human prostate cancer cells proliferation by a selective alpha1-adrenoceptor antagonist labedipinedilol-A involves cell cycle arrest and apoptosis. Toxicology. 2009;256:13–24.CrossRefGoogle Scholar
  33. 33.
    Gonzalez-Cabrera PJ, Shi T, Yun J, McCune DF, Rorabaugh BR, Perez DM. Differential regulation of the cell cycle by α1-adrenergic receptor subtypes. Endocrinology. 2004;145:5157–67.CrossRefGoogle Scholar
  34. 34.
    Kavelaars A. Regulated expression of alpha-1 adrenergic receptors in the immune system. Brain Behav Immun. 2002;16:799–807.CrossRefGoogle Scholar
  35. 35.
    Gramaglia I, Weinberg AD, Lemon M, Croft M. Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses. J Immunol. 1998;161:6510–7.Google Scholar
  36. 36.
    Thornton AM, Shevach EM. CD4+ CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med. 1998;188:287–96.CrossRefGoogle Scholar
  37. 37.
    Szabo G, Dolganiuc A, Mandrekar P, White B. Inhibition of antigen-presenting cell functions by alcohol: implications for hepatitis C virus infection. Alcohol. 2004;33:241–9.CrossRefGoogle Scholar
  38. 38.
    Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T. Regulatory T cells: how do they suppress immune responses? Int Immunol. 2009;21:1105–11.CrossRefGoogle Scholar
  39. 39.
    Kotthoff P, Heine A, Held SAE, Brossart P. Dexamethasone induced inhibition of Dectin-1 activation of antigen presenting cells is mediated via STAT-3 and NF-κB signaling pathways. Sci Rep. 2017;7:4522.CrossRefGoogle Scholar
  40. 40.
    Cosentino M, Fietta AM, Ferrari M, Rasini E, Bombelli R, Carcano E, et al. Human CD4+ CD25+ regulatory T cells selectively express tyrosine hydroxylase and contain endogenous catecholamines subserving an autocrine/paracrine inhibitory functional loop. Blood. 2007;109:632–42.CrossRefGoogle Scholar
  41. 41.
    Wang XQ, Liu Y, Cai HH, Peng YP, Qiu YH. Expression of tyrosine hydroxylase in CD4+ T cells contributes to alleviation of Th17/Treg imbalance in collagen-induced arthritis. Exp Biol Med. 2016;241:2094–103.CrossRefGoogle Scholar
  42. 42.
    Bhowmick S, Singh A, Flavell RA, Clark RB, O’Rourke J, Cone RE. The sympathetic nervous system modulates CD4+ FoxP3+ regulatory T cells via a TGF-β-dependent mechanism. J Leukoc Biol. 2009;86:1275–83.CrossRefGoogle Scholar
  43. 43.
    Zhang B, Chikuma S, Hori S, Fagarasan S, Honjo T. Nonoverlapping roles of PD-1 and FoxP3 in maintaining immune tolerance in a novel autoimmune pancreatitis mouse model. Proc Natl Acad Sci U S A. 2016;113:8490–5.CrossRefGoogle Scholar
  44. 44.
    Wu GF, Shindler KS, Allenspach EJ, Stephen TL, Thomas HL, Mikesell RJ, et al. Limited sufficiency of antigen presentation by dendritic cells in models of central nervous system autoimmunity. J Autoimmun. 2011;36:56–64.CrossRefGoogle Scholar
  45. 45.
    Flierl MA, Rittirsch D, Nadeau BA, Chen AJ, Sarma JV, Zetoune FS, et al. Phagocyte-derived catecholamines enhance acute inflammatory injury. Nature. 2007;449:721–5.CrossRefGoogle Scholar
  46. 46.
    Stojić-Vukanić Z, Nacka-Aleksić M, Pilipović I, Vujnović I, Blagojević V, Kosec D, et al. Aging diminishes the resistance of AO rats to EAE: putative role of enhanced generation of GM-CSF expressing CD4+ T cells in aged rats. Immun Ageing. 2015;12:16.CrossRefGoogle Scholar
  47. 47.
    McGeachy MJ, Cua DJ. Th17 cell differentiation: the long and winding road. Immunity. 2008;28:445–53.CrossRefGoogle Scholar
  48. 48.
    Shaked I, Hanna RN, Shaked H, Chodaczek G, Nowyhed HN, Tweet G, et al. Transcription factor Nr4a1 couples sympathetic and inflammatory cues in CNS-recruited macrophages to limit neuroinflammation. Nat Immunol. 2015;16:1228–34.CrossRefGoogle Scholar
  49. 49.
    Bao JY, Huang Y, Wang F, Peng YP, Qiu YH. Expression of α-AR subtypes in T lymphocytes and role of the α-ARs in mediating modulation of T cell function. Neuroimmunomodulation. 2007;14:344–53.CrossRefGoogle Scholar
  50. 50.
    Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, et al. Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. J Exp Med. 2003;198:1875–86.CrossRefGoogle Scholar
  51. 51.
    Huber S, Schramm C, Lehr HA, Mann A, Schmitt S, Becker C, et al. Cutting edge: TGF-β signaling is required for the in vivo expansion and immunosuppressive capacity of regulatory CD4+CD25+ T cells. J Immunol. 2004;173:6526–31.CrossRefGoogle Scholar
  52. 52.
    Fisher SA, Absher M. Norepinephrine and ANG II stimulate secretion of TGF-beta by neonatal rat cardiac fibroblasts in vitro. Am J Phys. 1995;268:C910–7.CrossRefGoogle Scholar
  53. 53.
    van der Voort CR, Kavelaars A, van de Pol M, Heijnen CJ. Neuroendocrine mediators up-regulate α1b-and α1d-adrenergic receptor subtypes in human monocytes. J Neuroimmunol. 1999;95:165–73.CrossRefGoogle Scholar
  54. 54.
    Dimitrijević M, Pilipović I, Stanojević S, Mitić K, Radojević K, Pešić V, et al. Chronic propranolol treatment affects expression of adrenoceptors on peritoneal macrophages and their ability to produce hydrogen peroxide and nitric oxide. J Neuroimmunol. 2009;211:56–65.CrossRefGoogle Scholar
  55. 55.
    Nijhuis LE, Olivier BJ, Dhawan S, Hilbers FW, Boon L, Wolkers MC, et al. Adrenergic β2 receptor activation stimulates anti-inflammatory properties of dendritic cells in vitro. PLoS One. 2014;9:e85086.CrossRefGoogle Scholar
  56. 56.
    Heijnen CJ, van der Voort CR, Wulffraat N, van der Net J, Kuis W, Kavelaars A. Functional α1-adrenergic receptors on leukocytes of patients with polyarticular juvenile rheumatoid arthritis. J Neuroimmunol. 1996;71:223–6.CrossRefGoogle Scholar
  57. 57.
    Hsu P, Santner-Nanan B, Hu M, Skarratt K, Lee CH, Stormon M, et al. IL-10 potentiates differentiation of human induced regulatory T cells via STAT3 and Foxo1. J Immunol. 2015;195:3665–74.CrossRefGoogle Scholar
  58. 58.
    Hetier E, Ayala J, Bousseau A, Prochiantz A. Modulation of interleukin-1 and tumor necrosis factor expression by β-adrenergic agonists in mouse ameboid microglial cells. Exp Brain Res. 1991;86:407–13.CrossRefGoogle Scholar
  59. 59.
    Veldhoen M, Moncrieffe H, Hocking RJ, Atkins CJ, Stockinger B. Modulation of dendritic cell function by naive and regulatory CD4+ T cells. J Immunol. 2006;176:6202–10.CrossRefGoogle Scholar
  60. 60.
    Hänig J, Lutz MB. Suppression of mature dendritic cell function by regulatory T cells in vivo is abrogated by CD40 licensing. J Immunol. 2008;180:1405–13.CrossRefGoogle Scholar
  61. 61.
    Taga K, Tosato G. IL-10 inhibits human T cell proliferation and IL-2 production. J Immunol. 1992;148:1143–8.Google Scholar
  62. 62.
    Neveu PJ, Merlot E. Cytokine stress responses depend on lateralization in mice. Stress. 2003;6:5–9.CrossRefGoogle Scholar
  63. 63.
    Manel N, Unutmaz D, Littman DR. The differentiation of human TH-17 cells requires transforming growth factor-β and induction of the nuclear receptor RORγt. Nat Immunol. 2008;9:641–9.CrossRefGoogle Scholar
  64. 64.
    Grisanti LA, Woster AP, Dahlman J, Sauter ER, Combs CK, Porter JE. α1-Adrenergic receptors positively regulate Toll-like receptor cytokine production from human monocytes and macrophages. J Pharmacol Exp Ther. 2011;338:648–57.CrossRefGoogle Scholar
  65. 65.
    Chaudhry A, Samstein RM, Treuting P, Liang Y, Pils MC, Heinrich JM, et al. Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity. 2011;34:566–78.CrossRefGoogle Scholar
  66. 66.
    Huber S, Gagliani N, Esplugues E, O’Connor W Jr, Huber FJ, Chaudhry A, et al. Th17 cells express interleukin-10 receptor and are controlled by Foxp3− and Foxp3+ regulatory CD4+ T cells in an interleukin-10-dependent manner. Immunity. 2011;34:554–65.CrossRefGoogle Scholar
  67. 67.
    Di Cesare A, Di Meglio P, Nestle FO. The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol. 2009;129:1339–50.CrossRefGoogle Scholar
  68. 68.
    Mufazalov IA, Schelmbauer C, Regen T, Kuschmann J, Wanke F, Gabriel LA, et al. IL-1 signaling is critical for expansion but not generation of autoreactive GM-CSF+ Th17 cells. EMBO J. 2017;36:102–15.CrossRefGoogle Scholar
  69. 69.
    Hartmann FJ, Khademi M, Aram J, Ammann S, Kockum I, Constantinescu C, et al. Multiple sclerosis-associated IL2RA polymorphism controls GM-CSF production in human TH cells. Nat Commun. 2014;5:5056.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ivan Pilipović
    • 1
  • Ivana Vujnović
    • 1
  • Zorica Stojić-Vukanić
    • 2
  • Raisa Petrović
    • 1
  • Duško Kosec
    • 1
  • Mirjana Nacka-Aleksić
    • 3
  • Nebojša Jasnić
    • 4
  • Gordana Leposavić
    • 3
    Email author
  1. 1.Immunology Research Centre “Branislav Janković”Institute of Virology, Vaccines and Sera “Torlak”BelgradeSerbia
  2. 2.Department of Microbiology and ImmunologyUniversity of Belgrade-Faculty of PharmacyBelgradeSerbia
  3. 3.Department of PathobiologyUniversity of Belgrade-Faculty of PharmacyBelgradeSerbia
  4. 4.Institute for Physiology and BiochemistryUniversity of Belgrade-Faculty of BiologyBelgradeSerbia

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