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Abstract
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-γ, 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.
| Abbreviations | ||
| BAFF/APRIL | = | B cell-activating factor of the TNF family/homolog A proliferation-inducing ligand |
| CTLA4 | = | cytotoxic T lymphocyte-associated antigen 4 |
| CTLA4Ig | = | CTLA4 linked to the Fc portion of IgG1 |
| FITC | = | fluorescein isothiocyanate |
| dsDNA | = | double-stranded DNA |
| MTT | = | 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide |
| PBS | = | phosphate-buffered saline |
| PE | = | phycoerythrin |
| SLE | = | systemic lupus erythematosus |
| Th1 | = | T helper cell type 1 |
| Th2 | = | T helper cell type 2 |
| Abbreviations | ||
| BAFF/APRIL | = | B cell-activating factor of the TNF family/homolog A proliferation-inducing ligand |
| CTLA4 | = | cytotoxic T lymphocyte-associated antigen 4 |
| CTLA4Ig | = | CTLA4 linked to the Fc portion of IgG1 |
| FITC | = | fluorescein isothiocyanate |
| dsDNA | = | double-stranded DNA |
| MTT | = | 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide |
| PBS | = | phosphate-buffered saline |
| PE | = | phycoerythrin |
| SLE | = | systemic lupus erythematosus |
| Th1 | = | T helper cell type 1 |
| Th2 | = | T helper cell type 2 |
Acknowledgements
This work was supported by a 211 Project scientific research grant (no. 98151) from Sun Yat-sen University School of Medical Sciences. The authors thank Dr Bin Hu (Da'an Gene Co. Ltd, Sun Yat-sen University, Guangzhou, China) and Mr Qing-Yu Kon (Department of Internal Medicine, Sun Yat-sen University, Guangzhou, China) for technical advice and assistance.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.