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.
Zhou
Yan-Bin
YB
Department of Internal Medicine, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. sumszyb@yahoo.com.cn
Ye
Ren-Gao
RG
Li
You-Ji
YJ
Xie
Can-Mao
CM
Wu
Yu-Hong
YH
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