T-cells from the blood and sites of inflammation. While effective, the FcR-binding antibodies deliver strong stimulatory signals to the T-cell, leading to activation-induced-cell-death, and largely depleting T-cells from the periphery and site of inflammation. This effect was transient, and mice were able to mount normal immune responses to exogenous antigens within weeks of treatment. However, treatment with FcR-binding anti-CD3 antibody such as OKT3 induced strong stimulation of T-cells, leading to T-cell cytokine release, which resulted in a number of symptoms when administered to patients. In lieu of this, a mutant version of the antibody was developed that lacked the ability to bind FcR. This mutant form of the anti-CD3 acts by only delivering a partial signal to the T-cell, leading to inactivation, deletion, and anergy induction. Results from a clinical trial in 2000 showed that treatment with the modified form of anti-CD3 preserved islet function in new-onset Type 1 diabetics. Data from follow up studies suggest that anti-CD3 antibody treatment caused not only anergy induction and transient depletion of T cells, but an increase in CD4+ and CD8+ Foxp3+Tregs. While promising, islet function gradually decreased over time in human patients treated with anti-CD3 antibodies, and data suggest that the mitogenic capabilities of anti-CD3 antibodies may overcome their therapeutic utility. Although current clinical trials are ongoing to improve the efficacy of anti-CD3 antibody treatment, alternative targets within the TCR may provide a better therapeutic T cell target. Campath-1H Although it is not thought to directly target components of the TCR/CD3 complex, Alemtuzumab, or Campath-1H, has been utilized because of its strong ability to deplete T cells, in many cases for up to 3 years. It is a monoclonal antibody that targets CD52, a protein that is expressed on the surface of mature lymphocytes. Originally approved for B cell cancers, its use has spread to off-label indications. One such indication includes renal transplantation, whereby its use remains controversial. This is not because the antibody is not extremely efficient at immune-suppressing patients, but due to the inherent risk of patients developing serious complications. Furthermore, the use of Alemtuzumab in transplantation may also be a question related to reimbursement, as it is comparably cheaper to other drugs used to treat clinical episodes of transplant rejection, and it can significantly shorten the duration of a patients hospital visit. Alemtuzumab is now being tested in clinical trials for the treatment of autoimmune diseases, such as Multiple