This research study is for patients who are going to receive a kidney transplant from a living donor. After kidney transplantation, it is necessary for transplant recipients to take "immunosuppressive drugs". These drugs work by preventing the body's immune cells from attacking and "rejecting" the new kidney. Taking these drugs long-term may also cause harm to the transplanted kidney. Therefore, the transplant community is very interested in finding ways to decrease immunosuppressive drug treatment and further reduce the risk of kidney rejection. One method to do so is known as "induction of tolerance", which is when the person who receives a transplant has treatment to make their immune cells tolerant to the donor cells.

In this study, we will try to induce tolerance by mixing recipient cells and their donor's cells together with belatacept, an immunosuppressive drug. Belatacept is a protein that attaches to immune system cells, interferes with the immune response and results in tolerance induction.

After we mix the recipient cells with the donor's cells, we will sort out one particular kind of immune cell, called a regulatory T cell, and inject them back into the recipient. Regulatory T cells are the cells that are affected by induction to reduce rejection of donated organs. This method for inducing tolerance has been used in bone marrow transplantation, but this is the first time it is being done in kidney transplantation.

This study is being conducted as part of a unique collaboration of US and EU centers called The ONE Study. The ONE Study centers have agreed to work together using common protocols and procedures but with each testing their own regulatory population for safety and the ability to promote kidney survival. Sharing data among the participating sites will permit a deeper understanding of how and why some treatments might succeed while others work less well.

Key Recipient Inclusion Criteria:

• Chronic renal insufficiency necessitating kidney transplantation
• Aged at least 18 years
• Donor is ABO (Blood type) compatible

Key Recipient Exclusion Criteria:

• HIV positive, EBV negative, or suffering from chronic viral hepatitis or tuberculosis
• Previously received any tissue or organ transplant other than planned kidney graft
• Genetically identical to the prospective organ donor at the HLA loci (0-0-0 mismatch)
• Panel Reactive Antibodies (PRA) >20%
• Concomitant malignancy or history of malignancy within 5 years prior to planned study entry (excluding successfully-treated non metastatic basal/squamous cell carcinoma of the skin)
• Ongoing treatment with systemic immunosuppressive drugs at study entry