A novel mechanism for induction of Tregs to control allergic disease
Abstract
In previous studies we reported immune regulation of colitis, transplanted tissue, and breast cancer in mice could be achieved by modifying immune networks using combinations of immune Ig and anti-idiotypic Ig. We have explored features of this regulation as it relates to altered allergic responses to ovalbumin, exploring attenuation of allergic reactivity in animals receiving combinations of either mouse or heterologous (human) Igs. Our data show a long-lasting suppression of allergic reactivity in mice (>14 weeks post cessation of treatment with Igs). This was seen both in mice receiving treatment from the time of allergen administration (suppression of induction of allergy), as well as in mice already sensitized to allergens before treatment began (suppression of pre-existing symptoms). In either case, attenuation of symptoms was abolished by infusion of T deleting antibodies during the time of Ig administration. Further confirming an importance for induction of (CD4+) Tregs in suppression of allergic responses, we showed that after enrichment, these cells derived from pre-immunized mice treated with combinations of Igs suppressed OVA-induced Th2 responses in cells from fresh populations of immunized animals in vitro. We hypothesize that this treatment regimen opens up new avenues of approach to the treatment of chronic allergic disease in man and in other animals.
Keywords
Full Text:
PDFReferences
Wheatley LM, Togias A Clinical Practice. Allergic rhinitis. The New England Journal of Medicine. 2015. 372 (5): 456–63.
Thomsen SF Atopic dermatitis: natural history, diagnosis, and treatment. "ISRN Allergy. 2014: 354250.
Pawankar R. Allergic diseases and asthma: a global public health concern and a call to action. World Allergy Organization Journal. 2014: 7:55: https://doi.org/10.1186/1939-4551-7-12
Nauta AJ. Mechanisms of allergy and asthma. Eur J Pharmacol 2008; 585:354-60.
Ciprandi G, Filaci G, Fenoglio D. Th17 cells and allergic rhinitis: Is there clinical relevance? Otolaryngol Head Neck Surg 2010; 143: 604-5.
Rivas MN, Chatila TA. Regulatory T cells in Allergic Diseases. J Allergy Clin Immunol 2016; 138:639-652.
Passalacqua G, Durham SR. Global Allergy and Asthma European Network. Allergic rhinitis and its impact on asthma update: allergen immunotherapy. J Allergy Clin Immunol 2007; 119(4):881-91.
Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens World Allergy Organ J. 2015; 8: 1-12.
Mohapatra SS, Qazi M, Hellermann G. Immunotherapy for allergies and asthma: present and future. Curr Opin Pharmacol 2010; 10(3):276-88.
Rolland JM, Gardner LM, O'Hehir RE. Functional regulatory T cells and allergen immunotherapy. Curr Opin Allergy Clin Immunol 2010; 10:559-66.
Canonica GW, Baena-Cagnani CE, Bousquet J, Bousquet PJ, Lockey RF, Malling HJ, et al. Recommendations for standardization of clinical trials with Allergen Specific Immunotherapy for respiratory allergy. A statement of a World Allergy Organization (WAO) taskforce. Allergy 2007; 62(3):317-24.
Bacher P, Scheffold A. The effect of regulatory T cells on tolerance to airborne allergens and allergen immunotherapy. J Allergy Clin Immunol 2018; 142:1697-1709
Palomares O. The role of regulatory T cells in IgE-mediated Food allergy. J Investig Allergol Clin Immunol. 2013; 23:371-382.
Calzada D, Baos S, Cremades L, Cardaba B. New treatments for allergy: Advances in peptide immunotherapy. Curr Med Chem 2018; 25:2215-2232
Simms E, Syed I, Rudulier C, Larche M. Nelson HS. Peptide immunotherapy; short but long lasting? Curr Treatment Options in Allergy 2015; 2:64-71.
Jerne, N. K "Towards a network theory of the immune system". Annales d'immunologie. 1974; 125C (1–2): 373–389. PMID 4142565.
Hoffmannn GW. Immune Network Theory. 2008 www.physics.ubc.ca/~Hoffmannn/ni.html.
Seledtsov VI, Seledtsova GV. A possible role for idiotype:anti-idiotype B-T cell interactions in maintaining immune memory. Front Immunol. 2017. https://doi.org/10.3389/fimmu.2017.00409
Hoffmann GW, Muller S, Kohler H. Towards an HIV vaccine based on immune network theory Curr Trends Immunology 2012; 13: 69-79
Hoffmann GW, Otto T, Grant M, Muller S, Kohler H. J Infectious Diseases & Preventive Medicine 2019: 7: Iss.2 No:190: 1-5
Dosenovic P, Pettersson A-K, Wall A, Thientosapol ES, Feng J, Weidle C, Bhullar K et al. Anti-idiotypic antibodies elicit anti-HIV-1-specific B cell responses. J Exp Med 2019; 216:2316-2330
Bancroft T, DeBuysscher BL, Weidle C, Schwartz A, Wall A, Gray M, Feng J et al. Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes. J Exp Med. 2019; 216: 2331-2347
Gorczynski RM and Hoffmannn GW. Towards a new kind of vaccine: a logical extension of the symmetrical immune network theory Interact J Med Res. 2017: PMID: 28879488. DOI: 10 2196/ijmr.7612
Schreiber TH, Wolf D, Tsai MS, Chirinos J, Deyev V V., Gonzalez L, et al. Therapeutic Treg expansion in mice by TNFRSF25 prevents allergic lung inflammation. J Clin Invest. 2010;120:3629–40
Gorczynski RM, Maqbool T, Hoffmann GW. Mechanism(s) of prolonged attenuation of allergic responses after modulation of idiotypic regulatory network. Allergy, Asthma & Clin Immunol. 2019: in press
Schaub A, von Gunten S, Vogel M, Wymann S, Rüegsegger M, Stadler BM, Spycher M, Simon HU, Miescher S. Dimeric IVIG contains natural anti-Siglec-9 autoantibodies and their anti-idiotypes. Allergy. 2011;66:1030-7.
Konova E, Atanasova M, Stoykov S, Velkova A, Shoenfeld Y. Idiotypic and anti-idiotypic elastin autoantibodies: Implications for IVIg and pregnancy loss. J Autoimmun. 2007;28:46-54.
Wu R, Shoenfeld Y, Sherer Y, Patnaik M, Matsuura E, Gilburd B, Koike T, Peter JB.
Anti-idiotypes to oxidized LDL antibodies in intravenous immunoglobulin preparations--possible immunomodulation of atherosclerosis.
Autoimmunity. 2003;36:91-7.
DeKeyser F, DeKeyser H, Kazatchkine MD, Rossi F, Dang H, Talal N. Pooled human immunoglobulins contain anti-idiotypes with reactivity against the SLE-associated 4B4 cross-reactive idiotype.Clin Exp Rheumatol. 1996;14:587-91.
Caccavo D, Vaccaro F, Ferri GM, Amoroso A, Bonomo L. Anti-idiotypes against antiphospholipid antibodies are present in normal polyspecific immunoglobulins for therapeutic use.J Autoimmun. 1994;7:537-48.
Dietrich G, Kaveri SV, Kazatchkine MD. Modulation of autoimmunity by intravenous immune globulin through interaction with the function of the immune/idiotypic network.Clin Immunol Immunopathol. 1992 Jan;62(1 Pt 2):S73-81. Review.
Gorczynski RM, Sadozai H, Zhu F, Khatri I. Effect of infusion of monoclonal antibodies to tumour necrosis factor-receptor super family 25 on graft rejection in allo-immune mice receiving autologous marrow transplantation. Immunology. 2017; 150:418-431.
Taraban VY, Ferdinand JR, Al-Shamkhani A. Expression of TNFRSF25 on conventional T cells and Tregs. J Clin Invest 2011; 121:463-4; author reply 5.
Gorczynski RM, Maqbool T, Hoffmann GW. Combined IMIG and Immune Ig attenuates allergic responses in Beagle dogs: submitted: 2019
Furue M, Yamamura K, Kido-Nakahara M, Nakahara T, Fukui Y. Emerging role of
interleukin-31 and interleukin-31 receptor in pruritus in atopic dermatitis. Allergy 2018; 73:29-36.
Weinstein SF, Katial R, Jayawardena S, Pirozzi G, Staudinger H, Eckert L, Joish VN, Amin N, Maroni J, Rowe P, Graham NMH, Teper A. Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma. J Allergy Clin Immunol. 2018; 142:171-177.
Iftikhar IH, Schimmel M, Bender W, Swenson C, Amrol D. Comparative Efficacy of Anti IL-4, IL-5 and IL-13 Drugs for Treatment of Eosinophilic Asthma: A Network Meta-analysis. Lung. 2018; 196:517-530.
Ohta K, Nagase H, Suzukawa M, Ohta S. Antibody therapy for the management of severe asthma with eosinophilic inflammation. Int Immunol. 2017; 29:337-343.
Wasserman RL. Personalized Therapy: Immunoglobulin Replacement for Antibody Deficiency. Immunol Allergy Clin North Am. 2019;39:95-111.
Restrepo-Jiménez P, Rodríguez Y, González P, Chang C, Gershwin ME, Anaya JM.
The immunotherapy of Guillain-Barré syndrome.Expert Opin Biol Ther. 2018;18:619-631.
Wasserman RL. Gammaplex® 5 and 10% in the treatment of primary immunodeficiency and chronic immune thrombocytopenic purpura.
Immunotherapy. 2017;9:1071-1088.
Pascall B, Thakker A, Foo Y, Thakker P. Immunoglobulin for Kawasaki disease: a 3-year retrospective audit. BMJ Paediatr Open. 2019;3:e000451. doi: 10.1136/bmjpo-2019-000451.
Wawrzycki B, Krasowska D, Pietrzak A, Szumilo J, Blazowski L, Pietraszek-Mamcarz J, Lotti T.Infantile bullous pemphigoid successfully treated with combined pulse corticosteroids and high-dose IVIG. Dermatol Ther. 2018 Sep;31(5):e12635. doi: 10.1111/dth.12635. Epub 2018 Sep 14.
Marcus N, Smuel K, Almog M, Prais D, Straussberg R, Landau D, Scheuerman O.
Successful Intravenous Immunoglobulin Treatment in Pediatric Severe DRESS Syndrome.J Allergy Clin Immunol Pract. 2018;6:1238-1242.
Antoon JW, Goldman JL, Shah SS, Lee B.
A Retrospective Cohort Study of the Management and Outcomes of Children Hospitalized with Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis.
J Allergy Clin Immunol Pract. 2019;7:244-250
Forbat E, Ali FR, Al-Niaimi F. Intravenous immunoglobulins in dermatology. Part 2: clinical indications and outcomes. Clin Exp Dermatol. 2018;43:659-666.
Maddur MS, Lacroix-Desmazes S, Dimitrov JD, Kazatchkine MD, Bayry J, Kaveri SV.
Natural Antibodies: from First-Line Defense Against Pathogens to Perpetual Immune Homeostasis. Clin Rev Allergy Immunol. 2019 Jun 3. doi: 10.1007/s12016-019-08746-9.
Lee SH, Ban GY, Kim SC, Chung CG, Lee HY, Lee JH, Park HS.
Association between primary immunodeficiency and asthma exacerbation in adult asthmatics. Korean J Intern Med. 2019 Jun 14. doi: 10.3904/kjim.2018.413.
Berger M, McCallus DE, Lin CS.Rapid and reversible responses to IVIG in autoimmune neuromuscular diseases suggest mechanisms of action involving competition with functionally important autoantibodies.J Peripher Nerv Syst. 2013;18:275-96.
Blank M, Bashi T, Shoenfeld Y.Idiotype-specific intravenous immunoglobulin (IVIG) for therapy of autoimmune diseases.Methods Mol Biol. 2014;1060:353-61.
Hong J, Xiao X,Gao Q, Li S, Jiang B, Sun X, Ran P, Yang P.Co-delivery of allergen epitope fragments and R848 inhibits food allergy by inducing tolerogenic dendritic cells and regulatory T cells. Int J Nanomedicine. 2019;14:7053-7064.
Wang M, Gu Z, Yang J, Zhao H, Cao Z.Changes among TGF-β1+ Breg cells and helper T cell subsets in a murine model of allergic rhinitis with prolonged OVA challenge. Int Immunopharmacol. 2019; 69:347-357.
Zissler UM, Jakwerth CA, Guerth FM, Pechtold L, Aguilar-Pimentel JA, Dietz K, Suttner K, Piontek G, Haller B, Hajdu Z, Schiemann M, Schmidt-Weber CB, Chaker AM.Early IL-10 producing B-cells and coinciding Th/Tr17 shifts during three year grass-pollen AIT. EBioMedicine. 2018;36:475-488.
Tsai YG, Yang KD, Wen YS, Hung CH, Chien JW, Lin CY.Allergen-specific immunotherapy enhances CD8+ CD25+ CD137+ regulatory T cells and decreases nasal nitric oxide. Pediatr Allergy Immunol. 2019;30:531-539.
Baumgartner-Nielsen J, Vestergaard C, Thestrup-Pedersen K, Deleuran M, Deleuran B.Glucocorticoid-induced tumour necrosis factor receptor (GITR) and its ligand (GITRL) in atopic dermatitis. Acta Derm Venereol. 2006;86:393-8.
Zhang M, Wan J, Xu Y, Zhang D, Peng J, Qi C, Guo Q, Xia S, Su Z, Wang S, Xu H.
Simultaneously increased expression of glucocorticoid induced tumor necrosis factor receptor and its ligand contributes to increased interleukin 5/13 producing group 2 innate lymphocytes in murine asthma. Mol Med Rep. 2017;15:4291-4299.
Nakajima-Adachi H, Shibahara K, Fujimura Y, Takeyama J, Hiraide E, Kikuchi A, Murakami H, Hosono A, Nochi T, Wakatsuki Y, Shimojo N, Kaminogawa S, Sato R, Kiyono H, Hachimura S. Critical role of intestinal interleukin-4 modulating regulatory T cells for desensitization, tolerance, and inflammation of food allergy. PLoS One. 2017 ;12(2): e0172795. doi: 10.1371/journal.pone.0172795.
Gorczynski RM, Farrokhi K, Sadozai H, Zhu F, and Khatri I. Importance of B cells to development of Tregs and prolongation of tissue allograft survival in recipients receiving autologous bone marrow transplantation. Immunology. 2018; 154:465-475
Wortel C, Heidt S. Regulatory B cells: Phenotype, function and role in transplantation. Transpl Immunol. 2017;41:1-9.
Goode I, Xu H, Ildstad ST. Regulatory B cells: The new “It” cell. Vol. 46, Transplantation Proceedings. 2014. p. 3–8.
Lee KM, Stott RT, Zhao G, Soohoo J, Xiong W, Lian MM, et al. TGF-β-producing regulatory B cells induce regulatory T cells and promote transplantation tolerance. Eur J Immunol. 2014;44(6):1728–36.
van de Veen W. The role of regulatory B cells in allergen immunotherapy. Curr Opin Allergy Clin Immunol. 2017;17:447-452.
Satitsuksanoa P, Jansen K, Głobińska A, van de Veen W, Akdis M Regulatory Immune Mechanisms in Tolerance to Food Allergy Front. Immunol., 2018; https://doi.org/10.3389/fimmu.2018.02939
Taitano SH, van der Vlugt LEPM, Shea MM, Jennifer Yang J, Nicholas W. Lukacs and Steven K. Lundy Differential Influence on Regulatory B Cells by TH2 Cytokines Affects Protection in Allergic Airway Disease J Immunol; 2018; 201:1865-1874.
DOI: http://dx.doi.org/10.18103/imr.v5i8.839
Refbacks
- There are currently no refbacks.