       Document 0704
 DOCN  M9630704
 TI    Preferential dependence of autoantibody production in murine lupus on
       CD86 costimulatory molecule.
 DT    9603
 AU    Nakajima A; Azuma M; Kodera S; Nuriya S; Terashi A; Abe M; Hirose S;
       Shirai T; Yagita H; Okumura K; Department of Immunology, Juntendo
       University School of Medicine,; Tokyo, Japan.
 SO    Eur J Immunol. 1995 Nov;25(11):3060-9. Unique Identifier : AIDSLINE
       MED/96085177
 AB    Blockade of the interactions between CD28/CTLA-4 and their ligands, CD80
       (B7, B7.1)/CD86 (B70, B7.2), seems an attractive means to induce
       antigen-specific peripheral tolerance in organ transplantation and
       autoimmune disease. Recently, diversities between CD80 and CD86 in
       expression, regulation, and function have been reported in certain cell
       populations and murine experimental disease models. To investigate the
       possible differential role of CD80 and CD86 in the development of lupus,
       we treated lupus-prone NZB/W F1 mice with specific monoclonal antibodies
       (mAb) against CD80, CD86, or both. The treatment with a combination of
       anti-CD80 and CD86 mAb before the onset of lupus completely prevented
       autoantibody production and nephritis, and prolonged survival.
       Interestingly, we found that anti-CD86 mAb alone, but not anti-CD80 mAb,
       efficiently inhibited autoantibody production. Subclass study on IgG
       anti-double-stranded (ds) DNA antibody revealed that the treatment with
       anti-CD86 mAb almost completely inhibited both IgG1 and IgG2b, but not
       IgG2a production. The incomplete reduction of IgG2a anti-dsDNA antibody
       by anti-CD86 mAb was compensated by the addition of anti-CD80 mAb. A
       significant reduction of mRNA for interleukin (IL)-2, interferon-gamma,
       IL-4 and IL-6 was observed in mice treated with a combination of
       anti-CD80 and CD86 mAb or anti-CD86 mAb alone. Treatment with both mAb
       after the onset of lupus resulted in a significantly prolonged survival
       with reduction of autoantibody production. These results suggest that
       CD86 plays a more critical role in autoantibody production, and CD86,
       but not CD80, contributes to Th2-mediated Ig production. However, the
       blockade of both CD80 and CD86 are required for preventing the
       development and progression of lupus.
 DE    Animal  Antibodies, Monoclonal/*THERAPEUTIC USE  Antigens,
       CD/*IMMUNOLOGY  Antigens, CD5/IMMUNOLOGY  Antigens, CD80/*IMMUNOLOGY
       Autoantibodies/*BIOSYNTHESIS/IMMUNOLOGY  B-Lymphocytes/IMMUNOLOGY
       Female  Lupus Erythematosus, Systemic/*IMMUNOLOGY/PREVENTION & CONTROL/
       THERAPY  Lupus Nephritis/IMMUNOLOGY/MORTALITY  Membrane
       Glycoproteins/*IMMUNOLOGY  Mice  Mice, Inbred BALB C  Mice, Inbred NZB
       Rats  Rats, Sprague-Dawley  Support, Non-U.S. Gov't  Th2
       Cells/IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

