ABSTRACT
T lymphocytes are essential for host defense against many viral or parasitic infections, and also contribute to defense against tumors. In addition, T cells mediate rejection o f transplanted organs, and, if inappropriately activated to recognize self-anti gens, can cause autoimmune diseases. Under normal conditions, the magnitude o f a T cell response rises and falls in a predictable fashion and the processes o f both activation and quiescence o f T lymphocytes are carefully regulated. T cell activation depends on recogni tion by the T cell receptor (TCR) o f specific antigenic peptide in the context o f major histocompatibility complex (M HC) molecules expressed by antigen presenting cells (APCs) such as dendritic cells, B cells, or macrophages. Additional signals delivered by costimulatory receptors such as C D 28 or tumor necrosis factor receptor (TN FR) family members are also required for complete T cell activation and differentiation to occur. Following T cell activation, inhibitory receptors such as CTLA-4 or the more recently described PD-11 become expressed, and can promote the termination o f an adaptive immune response. This chapter will focus on the regulation and function o f CTLA-4.
