期刊
AUTOIMMUNITY
卷 41, 期 5, 页码 395-404出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/08916930802002240
关键词
systemic lupus erythematosus; SLE; CD134 (OX40); CD134L (OX40L); anti-CD134L monoclonal antibody
类别
We sought to evaluate the effects of combined downregulation of CD134 and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) on the autoimmune process of lupus. Concanavalin A ( ConA)-induced proliferation, T helper cell cytokine secretion, and anti-double stranded DNA ( dsDNA) antibody production were measured in cultures of splenic lymphocytes derived from lupus-prone BXSB mice. Splenocytes from six prednisone-treated and six untreated male lupus-prone BXSB mice, as well as from six syngeneically normal C57BL/6 male mice, were stimulated with ConA. BXSB splenocytes from untreated mice were exposed to anti-CD134L mAb, CTLA4 linked to the Fc portion of IgG1 (CTLA4Ig), or both. The magnitude of splenocyte proliferation and the levels of IFN-gamma, IL-6, and anti-dsDNA antibody were: ( 1) significantly higher in cultures of ConA-stimulated control and other cells than in unstimulated cells, ( 2) similar in cultures of normal and BXSB cells treated with anti-CD134 and CTLA4Ig or prednisone and ( 3) significantly reduced in cultures of ConA-stimulated and unstimulated cells treated with anti-CD134L and CTLA4Ig or prednisone compared with cells treated with CD134L or CTLA4Ig alone. Like corticosteroids, anti-CD134L mAb or CTLA4Ig can inhibit T-and B-cell activation by blocking the CD134-CD134L or CD28/CTLA4-B7 co-stimulatory pathway. The combined immune intervention described herein may prove useful for the treatment of autoimmune diseases such as systemic lupus erythematosus.
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