ABSTRACT. Objective. To determine the immunomodulatory effects of the anti-rat CD28 monoclonal antibody (Mab) JJ316 on the onset of rat adjuvant arthritis (AA). JJ316 is a superagonistic Mab that induces polyclonal T cell proliferation in the absence of T cell receptor (TCR) ligation and promotes the expansion of regulatory T cells. Methods. Female Wistar rats in which AA was induced were treated with JJ316 on Day 0 and Day 9 postinduction. A parallel treatment with JJ319, a "conventional" CD28-specific Mab that costimulates anti-TCR triggered proliferation, was performed. Severity of arthritis was monitored by means of an arthritic score, and by recording hindpaw volume and body weight increases. Serum antibodies against the AA-inducing mycobacteria were also determined by ELISA. To ascertain the effect of JJ316 on T lymphocytes in vivo, blood CD4+CD45RC high (Th1-like) and CD4+CD45RC low (Th2-like) cells were analyzed by flow cytometry, and the relative levels of interleukin 2 (IL-2), IL-10, and interferon-γ (IFN-γ) mRNA in synovial tissue were measured by real-time reverse transcriptionpolymerase chain reaction. Results. JJ316 efficiently prevented the inflammatory process of AA. This effect was associated with a specific decrease in the blood CD4+CD45RC high /CD4+CD45RC low T cell ratio and high IL-10 mRNA expression in the synovia. In addition, anti-mycobacteria antibody levels decreased in JJ316 treated animals. In contrast, administration of the conventional anti-CD28 Mab JJ319 did not improve inflammation. Conclusion. JJ316, a stimulatory CD28-specific Mab known to promote Th2 function and the expansion of regulatory T cells, provides effective protection from AA. (J Rheumatol 2006;33:110-8
