Role of CD28 superagonist in preventing HSK lesions in mice

Abstract

Abstract Ocular infection with herpes simplex virus (HSV) can result in a chronic immune-inflammatory lesion that is a significant cause of human blindness. A key to controlling stromal keratitis (SK) lesion severity is to identify cellular and molecular events responsible for tissue damage. Regulatory T cells (Tregs) are known for preventing autoimmune diseases like systemic lupus erythematosus (SLE), multiple sclerosis (MS), Type 1 diabetes (T1D), rheumatoid arthritis (RA) and Inflammatory bowel disease (IBD). Furthermore, Tregs play an important role in reducing the severity of SK lesions by inhibiting the immune responses which cause immunopathology. In T cell activation and clonal expansion, the costimulatory receptor CD28 and its closest structural relative, the de-activating receptor CTLA-4 (CD152) are of central importance. Both bind to CD80 and CD86 expressed by APC. Interestingly, there is a class of “superagonistic” CD28 specific mAb which are able to preferentially expand and activate Tregs. Previous studies have shown that treating mice with a CD28 superagonistic antibody (CD28SA) ameliorated the acute signs of arthritis and completely prevented the development of chronic destructive arthritis in a mouse model. In the present study, we report that a single injection with CD28SA mAb given at day 3 post infection, reduced the severity of SK lesions. We found increased numbers of Tregs in mice treated with CD28SA. Additional mechanisms involved will be further evaluated during the course of the study. Thus, our studies demonstrate the usefulness of CD28SA as a therapeutic agent to control virus induced immunopathology.