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Epicutaneous (EC) immunization with type II collagen (COLL II) induces CD4+ CD8+ T suppressor cells that protect from collagen-induced arthritis (CIA)

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Abstract

Background

We have shown previously that epicutaneous (EC) immunization with protein antigen induces T suppressor cells that alleviate inflammatory response in contact hypersensitivity reactions, in an animal model of multiple sclerosis, and in TNBS-induced colitis.

Methods

DBA/1 mice were EC immunized with type II collagen (COLL II) spread over a gauze patch on days 0 and 4. On day 7, patches were removed and mice were intradermally (id) immunized with COLL II in CFA to induce collagen-induced arthritis (CIA).

Results

Our work shows that EC immunization with 100 μg of COLL II prior to CIA induction reduces disease severity as determined by macroscopic evaluation. Reduced disease severity after EC immunization with COLL II correlates with milder histological changes found in joint sections. Experiments with the three non-cross-reacting antigens COLL II, ovalbumin (OVA) and myelin basic protein (MBP) showed that skin-induced suppression is antigen non-specific. Transfer experiments show that EC immunization with COLL II induces suppressor cells that belong to the population of CD4+ CD8+ double positive lymphocytes. Flow cytometry experiments showed increased percentage of CD4+ CD8+ RORγt+ cells in axillary and inguinal lymph nodes isolated from mice patched with COLL II.

Conclusion

Maneuver of EC immunization with a protein antigen that induces suppressor cells to inhibit inflammatory responses may become an attractive, noninvasive, needle-free therapeutic method for different clinical situations.

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Abbreviations

Ab:

antibody

ALNC:

axillary and inguinal lymph node cells

anti-CPP:

Anti-cyclic citrullinated peptide

CFA:

complete Freund’s adjuvants

CHS:

contact hypersensitivity reactions

CIA:

collagen-induced arthritis

COLL II:

type II collagen

EAE:

experimental autoimmune encephalomyelitis

EC:

epicutaneous

FBS:

fetal bovine serum

id :

intradermally

IFA:

incomplete Freund’s adjuvants

Ig:

immunoglobulin

IL:

interleukin

ip :

intraperitoneally

iv :

intravenous

LPS:

lipopolysaccharide

MBP:

myelin basic protein

MPO:

myeloperoxidase

NK:

natural killer

NKT:

natural killer T cell

OVA:

ovalbumin

PBS:

phosphate buffered saline

RA:

rheumatoid arthritis

RC:

rabbit complement

TGF-β:

transforming growth factor beta

Tc:

T cytotoxic cell

Th:

T helper cell

TNBS-induced colitis:

the 2,4,6-trinitrobenzene sulfonic acid-induced colitis

TNP-Ig:

TNP conjugated mouse immunoglobulins

Ts:

T suppressor cell

References

  1. Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev 2005;4:130–6.

    Article  PubMed  Google Scholar 

  2. Chapel H, Haeney M, Misbah S, Snowden N. Essential of clinical immunology, 10. Oxford, United Kingdom: Blackwell Publishing Ltd.; 2006. p. 178–200.

    Google Scholar 

  3. Rap P, Knaus EE. Evolution of nonsteroidal anti-inflammatory drugs (NSAIDs): cyclooxygenase (COX) inhibition and beyond. J Pharm Pharm Sci 2008;11: 81–110.

    Article  Google Scholar 

  4. Vollenhoven RF. Treatment of rheumatoid arthritis: state of the art 2009. Nat Rev Rheumatol 2009;5:531–41.

    Article  Google Scholar 

  5. Mackenzie NM. New therapeutics that treat rheumatoid arthritis by blocking T-cell activation. Drug Discov Today 2006;11:952–6.

    Article  CAS  Google Scholar 

  6. Szczepanik M, Bryniarski K, Tutaj M, Ptak M, Skrzeczynska J, Askenase PW, et al. Epicutaneous immunization induces αβ T-cell receptor CD4 CD8 double-positive non-specific suppressor T cells that inhibit contact sensitivity via transforming growth factor-β. Immunology 2005;115:42–54.

    Article  CAS  PubMed  Google Scholar 

  7. Ptak W, Szczepanik M, Bryniarski K, Tutaj M, Ptak M. Epicutaneous application of protein antigens incorporated into cosmetic cream induces antigen-nonspecific unresponsiveness in mice and affects the cell-mediated immune response. Int Arch Allergy Immunol 2002;128:8–14.

    Article  PubMed  Google Scholar 

  8. Majewska-Szczepanik M, Zemelka-Wiacek M, Ptak W, Wen L, Szczepanik M. Epicutaneous immunization with DNP-BSA induces CD4+ CD25+ Treg cells that inhibit Tc1-mediated CS. Immunol Cell Biol 2012;90:784–95.

    Article  CAS  PubMed  Google Scholar 

  9. Zemelka-Wiącek M, Majewska-Szczepanik M, Ptak W, Szczepanik M. Epicutaneous immunization with protein antigen induces antigen-non-specific suppression of CD8T cell mediated contact sensitivity. Pharmacol Rep 2012;64:1485–96.

    Article  PubMed  Google Scholar 

  10. Majewska-Szczepanik M, Strzępa A, Dorożyńska I, Motyl S, Banach T, Szczepanik M. Epicutaneous immunization with hapten-conjugated protein antigen alleviates contact sensitivity mediated by three different types of effector cells. Pharmacol Rep 2012;64:919–26.

    Article  CAS  PubMed  Google Scholar 

  11. Szczepanik M, Tutaj M, Bryniarski K, Dittel BN. Epicutaneously induced TGF-beta-dependent tolerance inhibits experimental autoimmune encephalomyelitis. J Neuroimmunol 2005;164:105–14.

    Article  CAS  PubMed  Google Scholar 

  12. Tutaj M, Szczepanik M. Epicutaneous (EC) immunization with myelin basic protein (MBP) induces TCRαβ+ CD4+ CD8+ double positive suppressor cells that protect from experimental autoimmune encephalomyelitis (EAE). J Autoimmun 2007;28:208–15.

    Article  CAS  PubMed  Google Scholar 

  13. Majewska M, Zając K, Kubera M, Bryniarski K, Ptak M, Basta-Kaim A, et al. Effect of ovoalbumin on the survival of an H-Y incompatible skin graft in C57BL/6 mice. Pharmacol Rep 2006;58:439–42.

    Google Scholar 

  14. Majewska-Szczepanik M, Góralska M, Marcińska K, Zemelka-Wiącek M, Strzępa A, Dorożyńska I, et al. Epicutaneous immunization with protein antygen TNP-lg alleviates TNBS-induced colitis in mice. Pharmacol Rep 2012;64:1497–504.

    Article  PubMed  Google Scholar 

  15. Marcińska K, Majewska-Szczepanik M, Maresz K, Szczepanik M. Epicutaneous immunization with collagen induces TCRαβ T suppressor cells that inhibit collagen-induced arthritis. Int Arch Allergy Immunol 2015;166:121–34.

    Article  PubMed  Google Scholar 

  16. Szczepanik M, Lewis J, Geba GP, Ptak W, Askenase PW. Positive regulatory gamma delta T cells in contact sensitivity: augmented responses by in vivo treatment with anti-gamma delta monoclonal antibody, or anti-V gamma 5 or V delta 4. Immunol Invest 1998;27:1–15.

    Article  CAS  Google Scholar 

  17. Juryńczyk M, Walczak A, Jurewicz A, Jesionek-Kupnicka D, Szczepanik M, Selmaj K. lmmune regulation of multiple sclerosis by transdermally applied myelin peptides. Ann Neurol 2010;68:593–601.

    Google Scholar 

  18. Walczak A, Siger M, Ciach A, Szczepanik M, Selmaj K. Transdermal application of myelin peptides in multiple sclerosis treatment. JAMA Neurol 2013;70: 1105–9.

    Article  PubMed  Google Scholar 

  19. Hoyne GF, Lamb JR. Regulation of T cell function in mucosal tolerance. Immunol Cell Biol 1997;75:197–201.

    Article  CAS  Google Scholar 

  20. Stingl G, Koning F, Hamada H, Yokoyama WM, Tschachler E, Bluestone JA, et al. Thy-1+ dendritic epidermal cells express T3 antigen and the T-cell receptor gamma chain. Proc Natl Acad Sci USA 1987;84:4586–90.

    Article  CAS  Google Scholar 

  21. Chen Y, Inobe JI, Kuchroo VK, Baron JL, Janeway CA, Weiner HL. Oral tolerance in myelin basic protein T-cell receptor transgenic mice: suppression of autoimmune encephalomyelitis and dose-dependent induction of regulatory cells. Proc Natl Acad Sci USA 1996;93:388–91.

    Article  CAS  Google Scholar 

  22. Szczepanik M. Skin-induced tolerance as a new needle free therapeutic strategy. Pharmacol Rep 2014;66:192–7.

    Article  CAS  Google Scholar 

  23. Zhu S, Qian Y. IL-17/IL-17 receptor system in autoimmune disease: mechanism and therapeutic potential. Clin Sci (Lond) 2012;122:487–511.

    Article  CAS  Google Scholar 

  24. Nakae S, Nambu A, Sudo K, Iwakura Y. Suppression of immune induction of collagen-induced arthritis in IL-17 deficient mice. J Immunol 2003;171: 6173–7.

    Article  CAS  Google Scholar 

  25. Nakae S, Saijo S, Horai R, Sudo K, Mori S, Iwakura Y. IL-17 production from activated T cells is required for spontaneous development of destructive arthritis in mice deficient in IL-1 receptor agonist. Proc Natl Acad Sci USA 2003;100:5986–90.

    Article  CAS  Google Scholar 

  26. He R, Oyoshi MK, Jin H, Geha RS. Epicutaneous antigen exposure induces a Th17 response that drives airway inflammation after inhalation challenge. Proc Natl Acad Sci USA 2007;104:15817–22.

    Article  CAS  Google Scholar 

  27. Ogawa A, Andoh A, Araki Y, Bamba T, Fujiyama Y. Neutralization of interleukin-17 aggrevates dextran sulfate sodium-induced colitis in mice. Clin Immunol 2004;110:55–62.

    Article  CAS  Google Scholar 

  28. Schnyder-Candrian S, Togbe D, Couillin I, Mercier I, Brombacher F, Quesniaux V, et al. Interleukin-17 is a negative regulator of established allergic asthma. J Exp Med 2006;203:2715–25.

    Article  CAS  PubMed  Google Scholar 

  29. Pesenacker AM, Bending D, Ursu S, Wu Q, Nistala K, Wedderburn LR. CD161 defines the subset of FoxP3+ T cells capable of producing proinflammatory cytokines. Blood 2013;121:2647–58.

    Article  CAS  PubMed  Google Scholar 

  30. Afzali B, Mitchell PJ, Edozie FC, Povoleri GAM, Dowson SE, Demandt L, et al. CD161 expression characterizes a subpopulation of human regulatory T cells that produces IL-17 in a STAT-3- dependent manner. Eur J Immunol 2013;43:2043–54.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Biology, Jagiellonian University Medical College, Kraków, Poland

    Katarzyna Marcińska, Monika Majewska-Szczepanik, Paulina Kowalczyk, Dominika Biała, Dorota Woźniak & Marian Szczepanik

  2. Department of Pathomorphology, Jagiellonian University Medical College, Kraków, Poland

    Agata Lazar

Authors
  1. Katarzyna Marcińska
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  2. Monika Majewska-Szczepanik
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  3. Agata Lazar
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  4. Paulina Kowalczyk
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  7. Marian Szczepanik
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Correspondence to Marian Szczepanik.

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Marcińska, K., Majewska-Szczepanik, M., Lazar, A. et al. Epicutaneous (EC) immunization with type II collagen (COLL II) induces CD4+ CD8+ T suppressor cells that protect from collagen-induced arthritis (CIA). Pharmacol. Rep 68, 483–489 (2016). https://doi.org/10.1016/j.pharep.2015.11.004

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  • DOI: https://doi.org/10.1016/j.pharep.2015.11.004

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