ABSTRACT
T cell costimulation. Costimulation is defined as signals from membrane bound molecules that synergize with, or modify, signals provided when the T cell en counters its specific antigen. In large part, costimulation is essential for an effi cient T cell response, whether it is protective or pathogenic, and without costimulatory interactions between membrane bound receptor-ligand pairs, a T cell is ineffective and may often succumb to death or become nonfunctional. 0X40 is induced on the T cell surface a number of hours or days after recognition of antigen, and expression coincides with the appearance of OX40L on several cell types that can present antigen such as dendritic cells and В cells. Recent data show that 0X 40 can provide signals to a T cell to allow prolonged cell division after activation and to prevent excessive cell death. The OX40/OX40L interaction then controls the absolute number of pathogenic or protective effector T cells that are generated at the peak of the immune response and dictates the frequency of memory T cells that subsequently develop. This then has implications regarding strategies to suppress unwanted immune responses, and for vaccination to promote natu rally weak immune responses. Reagents that interfere with the binding of 0X40 to OX40L have been shown to inhibit T cell responses and pathogenic symptoms in a number of immune based diseases. Conversely reagents that augment 0X 40 signals have now shown therapeutic efficacy in models of cancer. This article will review the literature regarding these molecules and discuss their implications in T cell immunity.
