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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; 171(1):111-9CI

Abstract

Antigen-driven tolerance is an effective method of suppressing cell-mediated immune responses. We have previously demonstrated that exposure of gut-associated lymphoid tissue to myelin basic protein (MBP) via oral administration suppresses experimental autoimmune encephalomyelitis (EAE). To further study presentation of antigen to the immune system by mucosal surfaces as a method of antigen-driven tolerance, the effect of inhalation of MBP was investigated. MBP was given as an aerosol to Lewis rats on Days -10, -7, -5, and -3 prior to immunization with MBP in Freund's adjuvant and on Days 0, 2, and 4 following immunization. Aerosolization of MBP completely abrogated clinical EAE in 100% of treated rats. Central nervous system inflammation and delayed-type hypersensitivity and antibody responses to MBP were also significantly reduced in aerosol-treated animals. Aerosolization of histone, a basic protein of similar weight and charge as MBP, had no effect. Disease was also suppressed with one aerosol treatment on Day -3 or by administering MBP nasally. Aerosolization was more effective than oral administration of MBP over a wide dose range (0.005-5 mg). Splenic T cells isolated from animals postaerosolization adoptively transferred protection to naive animals immunized with MBP. Aerosolization of MBP to animals with relapsing EAE after recovery from the first attack decreased the severity of a subsequent attack. Aerosol and oral MBP were equally effective at suppressing the in vitro immune response as measured by proliferation and interferon-gamma production. We then tested aerosolization of a different autoantigen in a different disease model and found that aerosolization of type II collagen was effective in suppressing collagen-induced arthritis. Thus, aerosolization of an autoantigen is a potent method to downregulate an experimental T cell-mediated autoimmune disease and suggests that exposure of antigen to lung mucosal surfaces preferentially generates immunologic tolerance.

Authors+Show Affiliations

Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8660845

Citation

al-Sabbagh, A, et al. "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." Cellular Immunology, vol. 171, no. 1, 1996, pp. 111-9.
al-Sabbagh A, Nelson PA, Akselband Y, et al. 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;171(1):111-9.
al-Sabbagh, A., Nelson, P. A., Akselband, Y., Sobel, R. A., & Weiner, H. L. (1996). 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. Cellular Immunology, 171(1), pp. 111-9.
al-Sabbagh A, et al. 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. PubMed PMID: 8660845.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - al-Sabbagh,A, AU - Nelson,P A, AU - Akselband,Y, AU - Sobel,R A, AU - Weiner,H L, PY - 1996/7/10/pubmed PY - 1996/7/10/medline PY - 1996/7/10/entrez SP - 111 EP - 9 JF - Cellular immunology JO - Cell. Immunol. VL - 171 IS - 1 N2 - Antigen-driven tolerance is an effective method of suppressing cell-mediated immune responses. We have previously demonstrated that exposure of gut-associated lymphoid tissue to myelin basic protein (MBP) via oral administration suppresses experimental autoimmune encephalomyelitis (EAE). To further study presentation of antigen to the immune system by mucosal surfaces as a method of antigen-driven tolerance, the effect of inhalation of MBP was investigated. MBP was given as an aerosol to Lewis rats on Days -10, -7, -5, and -3 prior to immunization with MBP in Freund's adjuvant and on Days 0, 2, and 4 following immunization. Aerosolization of MBP completely abrogated clinical EAE in 100% of treated rats. Central nervous system inflammation and delayed-type hypersensitivity and antibody responses to MBP were also significantly reduced in aerosol-treated animals. Aerosolization of histone, a basic protein of similar weight and charge as MBP, had no effect. Disease was also suppressed with one aerosol treatment on Day -3 or by administering MBP nasally. Aerosolization was more effective than oral administration of MBP over a wide dose range (0.005-5 mg). Splenic T cells isolated from animals postaerosolization adoptively transferred protection to naive animals immunized with MBP. Aerosolization of MBP to animals with relapsing EAE after recovery from the first attack decreased the severity of a subsequent attack. Aerosol and oral MBP were equally effective at suppressing the in vitro immune response as measured by proliferation and interferon-gamma production. We then tested aerosolization of a different autoantigen in a different disease model and found that aerosolization of type II collagen was effective in suppressing collagen-induced arthritis. Thus, aerosolization of an autoantigen is a potent method to downregulate an experimental T cell-mediated autoimmune disease and suggests that exposure of antigen to lung mucosal surfaces preferentially generates immunologic tolerance. SN - 0008-8749 UR - https://www.unboundmedicine.com/medline/citation/8660845/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S000887499690180X DB - PRIME DP - Unbound Medicine ER -