Role of immunity and tolerance in renal diseases.

Dendritic cells (DC) have been recognized as the most efficient antigen presenting cells that have the capacity to initiate naive T-cell response in vitro and in vivo. During their differentiation and maturation pathways, DC can efficiently capture, process and present antigens for T-cell activation. These characteristics make DC an attractive choice as the cellular adjuvant for can-cer vaccines. In humans, two DC subsets, myeloid DC (mDC) and plasmacytoid DC (pDC), have been characterized and have distinct origins and functions: mDC are involved in the induction of the Th1 response, while pDC regulate immunity and initiate adaptive antiviral immune responses. Advances in DC generation, loading and maturation methodologies have made it possible to generate clinical grade vaccines for various human trials. Several studies have shown that tumor antigen-loaded DC vaccination is safe and promising for the treatment of cancer. We are investigating the use of autologous tumor lysate-pulsed mature DC in renal cancer patients with metastasis. DC can play a central role in the development of T-cell tolerance, and its maintenance in the periphery is critical for the prevention of autoimmunity. DC are likely to have a role in the pathogenesis of autoimmunity and are, to date, the only APC capable of provoking autoimmune disease. Systemic lupus erythematosus (SLE), a systemic autoimmune disease with multi-organ involvement with autoreactive T and B cells, could be due to DC alterations, and pDC have a potential role in this disease. Given their pivotal role in controlling immunity, DC are logical targets for treating both cancer and autoimmune diseases