Effect of anti-CD134L mAb and CTLA4Ig on ConA-induced proliferation, Th cytokine secretion, and anti-dsDNA antibody production in spleen cells from lupus-prone BXSB mice.
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.
Department of Internal Medicine, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. sumszyb@yahoo.com.cn
Yan-Bin
YB
Zhou
Ren-Gao
RG
Ye
You-Ji
YJ
Li
Can-Mao
CM
Xie
Yu-Hong
YH
Wu
D000069594:Abatacept; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003208:Concanavalin A; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D018796:Immunoconjugates / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D051379:Mice; D053278:OX40 Ligand / Q000276:immunology; D011241:Prednisone / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis; D053262:Receptors, OX40 / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D053278:OX40 Ligand; D012333:RNA, Messenger; D053262:Receptors, OX40; D003208:Concanavalin A; D000069594:Abatacept; D007371:Interferon-gamma; D011241:Prednisone