Transient blockade of CD40 ligand dissociates pathogenic from protective mucosal immunity.

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  • Additional Information
    • Source:
      Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print Cited Medium: Print ISSN: 0021-9738 (Print) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
    • Publication Information:
      Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
      Original Publication: New Haven [etc.] American Society for Clinical Investigation.
    • Subject Terms:
      CD40 Ligand/*immunology ; Immunity, Mucosal/*immunology ; T-Lymphocytes, Cytotoxic/*immunology; Administration, Oral ; Animals ; CD40 Antigens/genetics ; Diabetes Mellitus, Type 1/immunology ; Female ; Humans ; Immune Tolerance/immunology ; Interferon-gamma/biosynthesis ; Lymphocyte Activation/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Ovalbumin/administration & dosage ; Ovalbumin/immunology ; Signal Transduction/immunology
    • Abstract:
      Antigen administration via oral and other mucosal routes can suppress systemic immunity to the antigen and has been used to prevent experimental autoimmune disease. This approach may prove ineffective or even harmful if it leads to a concomitant induction of cytotoxic T lymphocytes (CTLs), and indeed, mucosal administration of the model antigen ovalbumin (OVA) has been shown to elicit CTL activation while simultaneously inducing oral tolerance. Here we show that induction by oral OVA of CTLs in wild-type mice, and of diabetes in mice expressing OVA transgenically in pancreatic beta cells, can be prevented by transiently blocking the CD40 ligand (CD40L). However, CD40L blockade did not diminish oral tolerance, as measured by suppression of systemic OVA-primed T cell proliferation, IFN-gamma secretion, and Ab production. Consistent with these findings, mice lacking CD40 expression could be orally tolerized to OVA. Transient CD40L blockade therefore dissociates pathogenic from protective immunity and should enhance the efficacy and safety of oral tolerance for preventing autoimmune disease.
    • Comments:
      Comment in: J Clin Invest. 2002 Jan;109(2):171-3. (PMID: 11805128)
    • References:
      Immunol Cell Biol. 1998 Feb;76(1):34-40. (PMID: 9553774)
      Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14626-31. (PMID: 9405663)
      Nature. 1998 Jun 4;393(6684):478-80. (PMID: 9624004)
      Nature. 1998 Jun 4;393(6684):480-3. (PMID: 9624005)
      J Exp Med. 1998 Jul 20;188(2):409-14. (PMID: 9670054)
      Diabetologia. 1998 Jul;41(7):844-7. (PMID: 9686928)
      J Exp Med. 1998 Dec 21;188(12):2205-13. (PMID: 9858507)
      J Immunol. 1999 Feb 15;162(4):1904-9. (PMID: 9973457)
      J Exp Med. 1999 Apr 5;189(7):1025-31. (PMID: 10190893)
      Arthritis Rheum. 1999 Jun;42(6):1204-8. (PMID: 10366113)
      Adv Immunol. 1999;73:153-264. (PMID: 10399007)
      J Immunol. 1999 Aug 15;163(4):2284-90. (PMID: 10438973)
      Diabetes. 2001 Apr;50(4):771-5. (PMID: 11289041)
      Nature. 1998 Jun 4;393(6684):474-8. (PMID: 9624003)
      J Exp Med. 1999 Nov 1;190(9):1275-84. (PMID: 10544199)
      J Immunol. 2000 May 1;164(9):4465-70. (PMID: 10779746)
      Lancet. 2000 Aug 12;356(9229):545-9. (PMID: 10950231)
      Diabetologia. 2000 Aug;43(8):1000-4. (PMID: 10990077)
      Curr Opin Immunol. 2000 Dec;12(6):704-11. (PMID: 11102776)
      Nature. 1990 Nov 22;348(6299):334-6. (PMID: 2250705)
      Science. 1993 Feb 26;259(5099):1321-4. (PMID: 7680493)
      Science. 1993 Sep 24;261(5129):1727-30. (PMID: 8378772)
      Cell. 1994 Jan 14;76(1):17-27. (PMID: 8287475)
      Eur J Immunol. 1994 May;24(5):1026-32. (PMID: 7514126)
      J Neuroimmunol. 1995 Feb;56(2):179-86. (PMID: 7860713)
      Immunity. 1994 Jun;1(3):167-78. (PMID: 7534202)
      Int Immunol. 1995 Mar;7(3):501-4. (PMID: 7794826)
      J Immunol. 1996 Feb 1;156(3):916-21. (PMID: 8558017)
      Ann N Y Acad Sci. 1996 Feb 13;778:418-21. (PMID: 8611008)
      J Exp Med. 1996 Feb 1;183(2):693-8. (PMID: 8627184)
      J Exp Med. 1996 May 1;183(5):2129-42. (PMID: 8642323)
      J Immunol. 1996 Sep 15;157(6):2348-57. (PMID: 8805632)
      Br J Rheumatol. 1996 Sep;35(9):828-38. (PMID: 8810665)
      Science. 1996 Dec 6;274(5293):1707-9. (PMID: 8939860)
      J Exp Med. 1997 Jul 7;186(1):65-70. (PMID: 9206998)
    • Accession Number:
      0 (CD40 Antigens)
      147205-72-9 (CD40 Ligand)
      82115-62-6 (Interferon-gamma)
      9006-59-1 (Ovalbumin)
    • Publication Date:
      Date Created: 20020124 Date Completed: 20020219 Latest Revision: 20181113
    • Publication Date:
      20231215
    • Accession Number:
      PMC150838
    • Accession Number:
      10.1172/JCI13720
    • Accession Number:
      11805138