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PMID: 9767428 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Dose-dependent mechanisms relate to nasal tolerance induction and protection against experimental autoimmune encephalomyelitis in Lewis rats.

Immunology ·Vol. 94 ·No. 3 ·1998-07-00 ·Pages 431-7

Li HL, Liu JQ, Bai XF, vn der Meide PH, Link H

Abstract

Nasal administration of soluble antigens is an exciting means of specifically down-regulating pathogenic T-cell reactivities in autoimmune diseases. The mechanisms by which nasal administration of soluble antigens suppresses autoimmunity are poorly understood. To define further the principles of nasal tolerance induction, we studied the effects of nasal administration of myelin basic protein (MBP) on experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. EAE is a CD4+ T-cell-mediated animal model for human multiple sclerosis. Nasal administration of guinea-pig (gp)-MBP at a dose as low as 30 micrograms/rat can completely prevent gp-MBP-induced EAE, whereas nasal administration of bovine (b)-MBP is not effective even at a much higher dosage. Cellular immune responses, as reflected by T-cell proliferation and interferon-gamma (IFN-gamma)-ELISPOT, were suppressed in rats receiving the two different doses (30 and 600 micrograms/rat) of gp-MBP, but not after administration of b-MBP. Rats tolerized with both doses of gp-MBP had also abrogated MBP-induced IFN-gamma mRNA expression in popliteal and inguinal lymph node mononuclear cells compared with rats receiving phosphate-buffered saline nasally. However, adoptive transfer revealed that only spleen mononuclear cells from rats pretreated with a low dose, but not from those pretreated with a high dose, of gp-MBP transferred protection to actively induced EAE. Low-dose (30 micrograms/rat) gp-MBP-tolerized rats also had high numbers of interleukin-4 (IL-4) mRNA-expressing lymph node cells, while high-dose (600 micrograms/rat) gp-MBP-tolerized rats had low numbers of IL-4 mRNA-expressing lymph node cells. Our data suggest an exquisite specificity of nasal tolerance. Dose-dependent mechanisms also relate to nasal tolerance induction and protection against EAE in the Lewis rat.

MeSH Terms
Administration, Intranasal Adoptive Transfer Animals Cattle Dose-Response Relationship, Immunologic Drug Administration Schedule Encephalomyelitis, Autoimmune, Experimental/immunology,prevention & control Guinea Pigs Immune Tolerance In Situ Hybridization Interferon-gamma/analysis,genetics Interleukin-4/genetics Lymph Nodes/immunology Myelin Basic Protein/administration & dosage RNA, Messenger/analysis Rats Rats, Inbred Lew Species Specificity T-Lymphocytes/immunology
Chemicals
Myelin Basic Protein RNA, Messenger Interleukin-4 Interferon-gamma
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Li H L
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Liu J Q
Bai X F
vn der Meide P H
Link H
References (46)
46 references, click to expand
  1. Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9-23).
    Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):956-60 PMID: 8570667
  2. Nasal administration of myelin basic protein prevents relapsing experimental autoimmune encephalomyelitis in DA rats by activating regulatory cells expressing IL-4 and TGF-beta mRNA.
    J Neuroimmunol. 1997 Dec;80(1-2):65-75 PMID: 9413260
  3. Antigen-specific immunotherapy of autoimmune disease: a commentary.
    Clin Exp Immunol. 1996 Mar;103(3):349-52 PMID: 8608630
  4. Mucosal tolerance and suppression of collagen-induced arthritis (CIA) induced by nasal inhalation of synthetic peptide 184-198 of bovine type II collagen (CII) expressing a dominant T cell epitope.
    Clin Exp Immunol. 1996 Mar;103(3):368-75 PMID: 8608633
  5. A few autoreactive cells in an autoimmune infiltrate control a vast population of nonspecific cells: a tale of smart bombs and the infantry.
    Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2253-6 PMID: 8637858
  6. Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes.
    J Exp Med. 1996 Apr 1;183(4):1561-7 PMID: 8666914
  7. Antigen-driven peripheral immune tolerance: suppression of experimental autoimmmune encephalomyelitis and collagen-induced arthritis by aerosol administration of myelin basic protein or type II collagen.
    Cell Immunol. 1996 Jul 10;171(1):111-9 PMID: 8660845
  8. Regulation of house dust mite responses by intranasally administered peptide: transient activation of CD4+ T cells precedes the development of tolerance in vivo.
    Int Immunol. 1996 Mar;8(3):335-42 PMID: 8671619
  9. Large scale preparation of myelin basic protein from central nervous tissue of several mammalian species.
    Prep Biochem. 1972;2(2):139-65 PMID: 4623901
  10. Production and assay of antibodies to acetylcholine receptors.
    Methods Enzymol. 1981;74 Pt C:432-60 PMID: 7321891
  11. Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein and its fragments.
    J Immunol. 1988 Jan 15;140(2):440-5 PMID: 2447178
  12. Suppression of experimental autoimmune encephalomyelitis by the oral administration of myelin basic protein.
    Cell Immunol. 1988 Apr 1;112(2):364-70 PMID: 2451570
  13. Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein. II. Suppression of disease and in vitro immune responses is mediated by antigen-specific CD8+ T lymphocytes.
    J Immunol. 1989 Feb 1;142(3):748-52 PMID: 2464023
  14. Defence against allergic sensitization in the healthy lung: the role of inhalation tolerance.
    Clin Exp Allergy. 1989 May;19(3):255-62 PMID: 2660967
  15. Structure and function of bronchus-associated lymphoid tissue (BALT).
    Crit Rev Immunol. 1989;9(2):119-50 PMID: 2663024
  16. Transforming growth factors beta 1 and beta 2: cytokines with identical immunosuppressive effects and a potential role in the regulation of autoimmune T cell function.
    J Neuroimmunol. 1989 Oct;24(3):249-58 PMID: 2808692
  17. Acetylcholine receptor-reactive T and B cells in myasthenia gravis and controls.
    J Clin Invest. 1991 Jun;87(6):2191-6 PMID: 1904073
  18. Oral tolerance in experimental autoimmune encephalomyelitis. III. Evidence for clonal anergy.
    J Immunol. 1991 Oct 1;147(7):2155-63 PMID: 1717550
  19. Antigen-driven bystander suppression after oral administration of antigens.
    J Exp Med. 1991 Oct 1;174(4):791-8 PMID: 1717632
  20. Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering.
    Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):421-5 PMID: 1370356
  21. The role of nasopharyngeal lymphoid tissue.
    Immunol Today. 1992 Jun;13(6):219-24 PMID: 1627250
  22. Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery.
    J Immunol. 1992 Oct 1;149(7):2496-505 PMID: 1527389
  23. Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor beta, interleukin 4, and prostaglandin E expression in the brain.
    J Exp Med. 1992 Nov 1;176(5):1355-64 PMID: 1383385
  24. Nasal administration of retinal antigens suppresses the inflammatory response in experimental allergic uveoretinitis. A preliminary report of intranasal induction of tolerance with retinal antigens.
    Br J Ophthalmol. 1993 Mar;77(3):171-5 PMID: 8457510
  25. Direct evidence for anergy in T lymphocytes tolerized by oral administration of ovalbumin.
    Eur J Immunol. 1993 Apr;23(4):935-42 PMID: 8458379
  26. The natural immune response to inhaled soluble protein antigens involves major histocompatibility complex (MHC) class I-restricted CD8+ T cell-mediated but MHC class II-restricted CD4+ T cell-dependent immune deviation resulting in selective suppression of immunoglobulin E production.
    J Exp Med. 1993 Sep 1;178(3):889-99 PMID: 8102390
  27. 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 Nov 1;178(5):1783-8 PMID: 8228823
  28. Epitopes of myelin basic protein that trigger TGF-beta release after oral tolerization are distinct from encephalitogenic epitopes and mediate epitope-driven bystander suppression.
    J Immunol. 1993 Dec 15;151(12):7307-15 PMID: 7505026
  29. Organ-specific autoantigens induce transforming growth factor-beta mRNA expression in mononuclear cells in multiple sclerosis and myasthenia gravis.
    Ann Neurol. 1994 Feb;35(2):197-203 PMID: 7509140
  30. Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals.
    Eur J Immunol. 1994 May;24(5):1026-32 PMID: 7514126
  31. Interleukin-10 prevents experimental allergic encephalomyelitis in rats.
    Eur J Immunol. 1994 Jun;24(6):1434-40 PMID: 7515815
  32. Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens.
    Annu Rev Immunol. 1994;12:809-37 PMID: 8011298
  33. Induction of anergy or active suppression following oral tolerance is determined by antigen dosage.
    Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6688-92 PMID: 8022835
  34. Induction of interferon-gamma, interleukin-4, and transforming growth factor-beta in rats orally tolerized against experimental autoimmune myasthenia gravis.
    Cell Immunol. 1994 Sep;157(2):353-68 PMID: 7520837
  35. Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease.
    J Exp Med. 1994 Nov 1;180(5):1961-6 PMID: 7525845
  36. Inhibition of T-cell responses by feeding peptides containing major and cryptic epitopes: studies with the Der p I allergen.
    Immunology. 1994 Oct;83(2):190-5 PMID: 7530688
  37. Suppression of experimental autoimmune myasthenia gravis by nasal administration of acetylcholine receptor.
    J Neuroimmunol. 1995 Apr;58(1):51-60 PMID: 7537280
  38. TGF-beta 2 decreases migration of lymphocytes in vitro and homing of cells into the central nervous system in vivo.
    J Immunol. 1995 Jul 1;155(1):325-32 PMID: 7602108
  39. Peripheral deletion of antigen-reactive T cells in oral tolerance.
    Nature. 1995 Jul 13;376(6536):177-80 PMID: 7603570
  40. Exquisite peptide specificity of oral tolerance in experimental autoimmune encephalomyelitis.
    J Immunol. 1995 Aug 1;155(3):1599-605 PMID: 7543526
  41. Treatment of experimental encephalomyelitis with a peptide analogue of myelin basic protein.
    Nature. 1996 Jan 25;379(6563):343-6 PMID: 8552189
  42. IL-10 fails to abrogate experimental autoimmune encephalomyelitis.
    J Neurosci Res. 1996 Sep 15;45(6):735-46 PMID: 8892085
  43. Aerosol insulin induces regulatory CD8 gamma delta T cells that prevent murine insulin-dependent diabetes.
    J Exp Med. 1996 Dec 1;184(6):2167-74 PMID: 8976172
  44. Regulation of T cell function in mucosal tolerance.
    Immunol Cell Biol. 1997 Apr;75(2):197-201 PMID: 9107576
  45. Oral tolerance: immune mechanisms and treatment of autoimmune diseases.
    Immunol Today. 1997 Jul;18(7):335-43 PMID: 9238837
  46. Mucosal tolerance to experimental autoimmune myasthenia gravis is associated with down-regulation of AChR-specific IFN-gamma-expressing Th1-like cells and up-regulation of TGF-beta mRNA in mononuclear cells.
    Ann N Y Acad Sci. 1996 Feb 13;778:273-87 PMID: 8610980
Article Info
Journal
Immunology
Abbr.
Immunology
ISSN
0019-2805
DOI
10.1046/j.1365-2567.1998.00526.x
Published
1998-07-00
Pages
431-7
Language
English
Region
England
NLM ID
0374672
PMCID
PMC1364264
Subset
IM
External Links
PubMed source DOI: 10.1046/j.1365-2567.1998.00526.x PMC Full Text View journal details
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