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BMC Immunology
Published in: BMC Immunology 1/2012

Open Access 01-12-2012 | Research article

Synthesized OVA323-339MAP octamers mitigate OVA-induced airway inflammation by regulating Foxp3 T regulatory cells

Authors: Wen Su, Wenwei Zhong, Yanjie Zhang, Zhenwei Xia

Published in: BMC Immunology | Issue 1/2012

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Abstract

Background

Antigen-specific immunotherapy (SIT) has been widely practiced in treating allergic diseases such as asthma. However, this therapy may induce a series of allergic adverse events during treatment. Peptide immunotherapy (PIT) was explored to overcome these disadvantages. We confirmed that multiple antigen peptides (MAPs) do not cause autoimmune responses, which led to the presumption that MAPs intervention could alleviate allergic airway inflammation without inducing adverse effects.

Results

In this study, synthesized OVA323-339MAP octamers were subcutaneously injected into ovalbumin (OVA)-sensitized and -challenged Balb/c mice to observe its effect on allergic airway inflammation, Th2 immune response, and immune regulating function. It was confirmed that OVA sensitization and challenge led to significant peritracheal inflammatory, cell infiltration, and intensive Th2 response. Treatment of OVA323-339MAP octomers in the airway inflammation mice model increased CD4+CD25+Foxp3+ T regulatory (Treg) cells and their regulatory function in peripheral blood, mediastinal draining lymph nodes, and the spleen. Furthermore, OVA323-339MAP increased IL-10 levels in bronchial alveolar lavage fluid (BALF); up-regulated the expression of IL-10, membrane-bound TGF-β1, as well as Foxp3 in lung tissues; and up-regulated programmed death-1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) on the surface of Treg cells. These results were further correlated with the decreased OVA specific immunoglobulin E (sIgE) level and the infiltration of inflammatory cells such as eosinophils and lymphocytes in BALF. However, OVA323-339 peptide monomers did not show any of the mentioned effects in the same animal model.

Conclusions

Our study indicates that OVA323-339MAP had significant therapeutic effects on mice allergic airway inflammation by regulating the balance of Th1/Th2 response through Treg cells in vivo.
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Literature
1.
Larche M: Peptide immunotherapy for allergic diseases. Allergy. 2007, 62: 325-331. 10.1111/j.1398-9995.2006.01309.x.PubMedCrossRef
2.
Pipet A, Botturi K, Pinot D, Vervloet D, Magnan A: Allergen-specific immunotherapy in allergic rhinitis and asthma. Mechanisms and proof of efficacy. Respir Med. 2009, 103: 800-812. 10.1016/j.rmed.2009.01.008.PubMedCrossRef
3.
Durham SR, Walker SM, Varga EM, Jacobson MR, O'Brien F, Noble W, Till SJ, Hamid QA, Nouri-Aria KT: Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med. 1999, 341: 468-475. 10.1056/NEJM199908123410702.PubMedCrossRef
4.
Briner TJ, Kuo MC, Keating KM, Rogers BL, Greenstein JL: Peripheral T-cell tolerance induced in naive and primed mice by subcutaneous injection of peptides from the major cat allergen Fel d I. Proc Natl Acad Sci U S A. 1993, 90: 7608-7612. 10.1073/pnas.90.16.7608.PubMedPubMedCentralCrossRef
5.
Hoyne GF, O'Hehir RE, Wraith DC, Thomas WR, Lamb JR: Inhibition of T cell and antibody responses to house dust mite allergen by inhalation of the dominant T cell epitope in naive and sensitized mice. J Exp Med. 1993, 178: 1783-1788. 10.1084/jem.178.5.1783.PubMedCrossRef
6.
Bauer L, Bohle B, Jahn-Schmid B, Wiedermann U, Daser A, Renz H, Kraft D, Ebner C: Modulation of the allergic immune response in BALB/c mice by subcutaneous injection of high doses of the dominant T cell epitope from the major birch pollen allergen Bet v 1. Clin Exp Immunol. 1997, 107: 536-541. 10.1046/j.1365-2249.1997.d01-953.x.PubMedPubMedCentralCrossRef
7.
King TP, Lu G, Agosto H: Antibody responses to bee melittin (Api m 4) and hornet antigen 5 (Dol m 5) in mice treated with the dominant T-cell epitope peptides. J Allergy Clin Immunol. 1998, 101: 397-403. 10.1016/S0091-6749(98)70254-4.PubMedCrossRef
8.
Norman PS, Ohman JL, Long AA, Creticos PS, Gefter MA, Shaked Z, Wood RA, Eggleston PA, Hafner KB, Rao P: Treatment of cat allergy with T-cell reactive peptides. Am J Respir Crit Care Med. 1996, 154: 1623-1628.PubMedCrossRef
9.
Pene J, Desroches A, Paradis L, Lebel B, Farce M, Nicodemus CF, Yssel H, Bousquet J: Immunotherapy with Fel d 1 peptides decreases IL-4 release by peripheral blood T cells of patients allergic to cats. J Allergy Clin Immunol. 1998, 102: 571-578. 10.1016/S0091-6749(98)70294-5.PubMedCrossRef
10.
Oldfield WL, Kay AB, Larche M: Allergen-derived T cell peptide-induced late asthmatic reactions precede the induction of antigen-specific hyporesponsiveness in atopic allergic asthmatic subjects. J Immunol. 2001, 167: 1734-1739.PubMedCrossRef
11.
Oldfield WL, Larche M, Kay AB: Effect of T-cell peptides derived from Fel d 1 on allergic reactions and cytokine production in patients sensitive to cats: a randomised controlled trial. Lancet. 2002, 360: 47-53. 10.1016/S0140-6736(02)09332-7.PubMedCrossRef
12.
Alexander C, Ying S, Ying S, B Kay A, Larche M: Fel d 1-derived T cell peptide therapy induces recruitment of CD4+ CD25+; CD4+ interferon-gamma + T helper type 1 cells to sites of allergen-induced late-phase skin reactions in cat-allergic subjects. Clin Exp Allergy : J British Soc Allergy Clin Immunol. 2005, 35: 52-58. 10.1111/j.1365-2222.2005.02143.x.CrossRef
13.
Worm M, Lee HH, Kleine-Tebbe J, Hafner RP, Laidler P, Healey D, Buhot C, Verhoef A, Maillere B, Kay AB: Development and preliminary clinical evaluation of a peptide immunotherapy vaccine for cat allergy. J Allergy Clin Immunol. 2011, 127: 89-97. 10.1016/j.jaci.2010.11.029. 97 e81-14PubMedCrossRef
14.
Alexander C, Tarzi M, Larche M, Kay AB: The effect of Fel d 1-derived T-cell peptides on upper and lower airway outcome measurements in cat-allergic subjects. Allergy. 2005, 60: 1269-1274. 10.1111/j.1398-9995.2005.00885.x.PubMedCrossRef
15.
Janssen EM, Wauben MH, Jonker EH, Hofman G, Van Eden W, Nijkamp FP, Van Oosterhout AJ: Opposite effects of immunotherapy with ovalbumin and the immunodominant T-cell epitope on airway eosinophilia and hyperresponsiveness in a murine model of allergic asthma. Am J Respir Cell Mol Biol. 1999, 21: 21-29.PubMedCrossRef
16.
Wegmann KW, Wagner CR, Whitham RH, Hinrichs DJ: Synthetic Peptide dendrimers block the development and expression of experimental allergic encephalomyelitis. J Immunol. 2008, 181: 3301-3309.PubMedCrossRef
17.
Mahajan B, Berzofsky JA, Boykins RA, Majam V, Zheng H, Chattopadhyay R, de la Vega P, Moch JK, Haynes JD, Belyakov IM: Multiple antigen peptide vaccines against Plasmodium falciparum malaria. Infect Immun. 2010, 78: 4613-4624. 10.1128/IAI.00533-10.PubMedPubMedCentralCrossRef
18.
Zhao G, Sun S, Du L, Xiao W, Ru Z, Kou Z, Guo Y, Yu H, Jiang S, Lone Y: An H5N1 M2e-based multiple antigenic peptide vaccine confers heterosubtypic protection from lethal infection with pandemic 2009 H1N1 virus. Virol J. 2010, 7: 151-10.1186/1743-422X-7-151.PubMedPubMedCentralCrossRef
19.
Haro I, Perez S, Garcia M, Chan WC, Ercilla G: Liposome entrapment and immunogenic studies of a synthetic lipophilic multiple antigenic peptide bearing VP1 and VP3 domains of the hepatitis A virus: a robust method for vaccine design. FEBS Lett. 2003, 540: 133-140. 10.1016/S0014-5793(03)00249-7.PubMedCrossRef
20.
Mozdzanowska K, Feng J, Eid M, Kragol G, Cudic M, Otvos L, Gerhard W: Induction of influenza type A virus-specific resistance by immunization of mice with a synthetic multiple antigenic peptide vaccine that contains ectodomains of matrix protein 2. Vaccine. 2003, 21: 2616-2626. 10.1016/S0264-410X(03)00040-9.PubMedCrossRef
21.
Franke ED, Sette A, Sacci J, Southwood S, Corradin G, Hoffman SL: A subdominant CD8(+) cytotoxic T lymphocyte (CTL) epitope from the Plasmodium yoelii circumsporozoite protein induces CTLs that eliminate infected hepatocytes from culture. Infect Immun. 2000, 68: 3403-3411. 10.1128/IAI.68.6.3403-3411.2000.PubMedPubMedCentralCrossRef
22.
Kawamura KS, Su RC, Nguyen LT, Elford AR, Ohashi PS, Gariepy J: In vivo generation of cytotoxic T cells from epitopes displayed on peptide-based delivery vehicles. J Immunol. 2002, 168: 5709-5715.PubMedCrossRef
23.
Verhoef A, Alexander C, Kay AB, Larche M: T cell epitope immunotherapy induces a CD4+ T cell population with regulatory activity. PLoS Med. 2005, 2: e78-10.1371/journal.pmed.0020078.PubMedPubMedCentralCrossRef
24.
Smith TR, Alexander C, Kay AB, Larche M, Robinson DS: Cat allergen peptide immunotherapy reduces CD4(+) T cell responses to cat allergen but does not alter suppression by CD4(+) CD25(+) T cells: a double-blind placebo-controlled study. Allergy. 2004, 59: 1097-1101. 10.1111/j.1398-9995.2004.00601.x.PubMedCrossRef
25.
Xia ZW, Xu LQ, Zhong WW, Wei JJ, Li NL, Shao J, Li YZ, Yu SC, Zhang ZL: Heme Oxygenase-1 Attenuates Ovalbumin-Induced Airway Inflammation by Up-Regulation of Foxp3 T-Regulatory Cells, Interleukin-10, and Membrane-Bound Transforming Growth Factor- 1. Am J Pathol. 2007, 171: 1904-1914. 10.2353/ajpath.2007.070096.PubMedPubMedCentralCrossRef
26.
Xia ZW, Zhong WW, Xu LQ, Sun JL, Shen QX, Wang JG, Shao J, Li YZ, Yu SC: Heme oxygenase-1-mediated CD4 + CD25high regulatory T cells suppress allergic airway inflammation. J Immunol. 2006, 177: 5936-5945.PubMedCrossRef
27.
Robertson JM, Jensen PE, Evavold BD: DO11.10 and OT-II T cells recognize a C-terminal ovalbumin 323-339 epitope. J Immunol. 2000, 164: 4706-4712.PubMedCrossRef
28.
Renz H, Bradley K, Larsen GL, McCall C, Gelfand EW: Comparison of the allergenicity of ovalbumin and ovalbumin peptide 323-339. Differential expansion of V beta-expressing T cell populations. J Immunol. 1993, 151: 7206-7213.PubMed
29.
Tam JP: Recent advances in multiple antigen peptides. J Immunol Methods. 1996, 196: 17-32. 10.1016/0022-1759(96)00066-X.PubMedCrossRef
30.
Rolland J, O’Hehir R: Immunotherapy of allergy: anergy, deletion, and immune deviation. Curr Opin Immunol. 1998, 10: 640-645. 10.1016/S0952-7915(98)80082-4.PubMedCrossRef
31.
Gardner LM, O'Hehir RE, Rolland JM: High dose allergen stimulation of T cells from house dust mite-allergic subjects induces expansion of IFN-gamma + T Cells, apoptosis of CD4 + IL-4+ T cells and T cell anergy. Int Arch Allergy Immunol. 2004, 133: 1-13. 10.1159/000075248.PubMedCrossRef
32.
Antunez C, Mayorga C, Corzo JL, Jurado A, Torres MJ: Two year follow-up of immunological response in mite-allergic children treated with sublingual immunotherapy. Comparison with subcutaneous administration. Pediatr Allergy Immunol: official publication of the Eur Soc Pediatr Allergy Immunol. 2008, 19: 210-218.CrossRef
33.
Akdis CA, Blesken T, Akdis M, Wuthrich B, Blaser K: Role of interleukin 10 in specific immunotherapy. J Clin Invest. 1998, 102: 98-106. 10.1172/JCI2250.PubMedPubMedCentralCrossRef
34.
Jutel M, Jaeger L, Suck R, Meyer H, Fiebig H, Cromwell O: Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol. 2005, 116: 608-613. 10.1016/j.jaci.2005.06.004.PubMedCrossRef
35.
Reisinger J, Horak F, Pauli G, van Hage M, Cromwell O, Konig F, Valenta R, Niederberger V: Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J Allergy Clin Immunol. 2005, 116: 347-354. 10.1016/j.jaci.2005.04.003.PubMedCrossRef
36.
Golden DB, Meyers DA, Kagey-Sobotka A, Valentine MD, Lichtenstein LM: Clinical relevance of the venom-specific immunoglobulin G antibody level during immunotherapy. J Allergy Clin Immunol. 1982, 69: 489-493. 10.1016/0091-6749(82)90172-5.PubMedCrossRef
37.
Muller U, Helbling A, Bischof M: Predictive value of venom-specific IgE, IgG and IgG subclass antibodies in patients on immunotherapy with honey bee venom. Allergy. 1989, 44: 412-418. 10.1111/j.1398-9995.1989.tb04172.x.PubMedCrossRef
38.
Taylor A, Akdis M, Joss A, Akkoc T, Wenig R, Colonna M, Daigle I, Flory E, Blaser K, Akdis CA: IL-10 inhibits CD28 and ICOS costimulations of T cells via src homology 2 domain-containing protein tyrosine phosphatase 1. J Allergy Clin Immunol. 2007, 120: 76-83. 10.1016/j.jaci.2007.04.004.PubMedCrossRef
39.
Akdis CA, Akdis M: Mechanisms and treatment of allergic disease in the big picture of regulatory T cells. J Allergy Clin Immunol. 2009, 123: 735-746. 10.1016/j.jaci.2009.02.030. quiz 747-738PubMedCrossRef
40.
Tarzi M, Klunker S, Texier C, Verhoef A, Stapel SO, Akdis CA, Maillere B, Kay AB, Larche M: Induction of interleukin-10 and suppressor of cytokine signalling-3 gene expression following peptide immunotherapy. Clin Exp Allergy: J British Soc Allergy Clin Immunol. 2006, 36: 465-474. 10.1111/j.1365-2222.2006.02469.x.CrossRef
41.
Campbell JD, Buckland KF, McMillan SJ, Kearley J, Oldfield WL, Stern LJ, Gronlund H, van Hage M, Reynolds CJ, Boyton RJ: Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression. J Exp Med. 2009, 206: 1535-1547. 10.1084/jem.20082901.PubMedPubMedCentralCrossRef
42.
Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM: Conversion of peripheral CD4 + CD25- naive T cells to CD4 + CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003, 198: 1875-1886. 10.1084/jem.20030152.PubMedPubMedCentralCrossRef
43.
Huber S, Schramm C, Lehr HA, Mann A, Schmitt S, Becker C, Protschka M, Galle PR, Neurath MF, Blessing M: Cutting edge: TGF-beta signaling is required for the in vivo expansion and immunosuppressive capacity of regulatory CD4 + CD25+ T cells. J Immunol. 2004, 173: 6526-6531.PubMedCrossRef
44.
Ostroukhova M, Seguin-Devaux C, Oriss TB, Dixon-McCarthy B, Yang L, Ameredes BT, Corcoran TE, Ray A: Tolerance induced by inhaled antigen involves CD4(+) T cells expressing membrane-bound TGF-beta and FOXP3. J Clin Invest. 2004, 114: 28-38.PubMedPubMedCentralCrossRef
45.
Ostroukhova M, Qi Z, Oriss TB, Dixon-McCarthy B, Ray P, Ray A: Treg-mediated immunosuppression involves activation of the Notch-HES1 axis by membrane-bound TGF-beta. J Clin Invest. 2006, 116: 996-1004. 10.1172/JCI26490.PubMedPubMedCentralCrossRef
46.
Takahashi T, Tagami T, Yamazaki S, Uede T, Shimizu J, Sakaguchi N, Mak TW, Sakaguchi S: Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med. 2000, 192: 303-310. 10.1084/jem.192.2.303.PubMedPubMedCentralCrossRef
47.
Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH: Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity. 1995, 3: 541-547. 10.1016/1074-7613(95)90125-6.PubMedCrossRef
48.
Radhakrishnan S, Iijima K, Kobayashi T, Rodriguez M, Kita H, Pease LR: Blockade of allergic airway inflammation following systemic treatment with a B7-dendritic cell (PD-L2) cross-linking human antibody. J Immunol. 2004, 173: 1360-1365.PubMedCrossRef
49.
Oflazoglu E, Swart DA, Anders-Bartholo P, Jessup HK, Norment AM, Lawrence WA, Brasel K, Tocker JE, Horan T, Welcher AA: Paradoxical role of programmed death-1 ligand 2 in Th2 immune responses in vitro and in a mouse asthma model in vivo. Eur J Immunol. 2004, 34: 3326-3336. 10.1002/eji.200425197.PubMedCrossRef
50.
Mann-Chandler MN, Kashyap M, Wright HV, Norozian F, Barnstein BO, Gingras S, Parganas E, Ryan JJ: IFN-gamma induces apoptosis in developing mast cells. J Immunol. 2005, 175: 3000-3005.PubMedCrossRef
51.
Kim HK, Guan H, Zu G, Li H, Wu L, Feng X, Elmets C, Fu Y, Xu H: High-level expression of B7-H1 molecules by dendritic cells suppresses the function of activated T cells and desensitizes allergen-primed animals. J Leukoc Biol. 2006, 79: 686-695. 10.1189/jlb.0805436.PubMedCrossRef
52.
Piconi S, Trabattoni D, Saresella M, Iemoli E, Schenal M, Fusi A, Borelli M, Chen L, Mascheri A, Clerici M: Effects of specific immunotherapy on the B7 family of costimulatory molecules in allergic inflammation. J Immunol. 2007, 178: 1931-1937.PubMedCrossRef
53.
Vargaftig BB, Singer M: Leukotrienes mediate part of Ova-induced lung effects in mice via EGFR. Am J Physiol Lung Cell Mol Physiol. 2003, 285: L808-L818.PubMedCrossRef
54.
Myou S, Leff AR, Myo S, Boetticher E, Tong J, Meliton AY, Liu J, Munoz NM, Zhu X: Blockade of inflammation and airway hyperresponsiveness in immune-sensitized mice by dominant-negative phosphoinositide 3-kinase-TAT. J Exp Med. 2003, 198: 1573-1582. 10.1084/jem.20030298.PubMedPubMedCentralCrossRef
Metadata
Title
Synthesized OVA323-339MAP octamers mitigate OVA-induced airway inflammation by regulating Foxp3 T regulatory cells
Authors
Wen Su
Wenwei Zhong
Yanjie Zhang
Zhenwei Xia
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2012
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/1471-2172-13-34

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