Costimulation: critical pathways in the immunologic regulation of asthma

T cells play an important role in the pathogenesis of allergy and asthma. T-cell receptor engagement by antigenic peptides presented to major histocompatibility complex (MHC) class II molecules and activation of costimulatory molecules are crucial in the regulation of T-cell immune responses. Costimulatory molecules are responsible for second signals that induce T-cell activation and proliferation. The best characterized costimulatory pathways include CD80/CD86 interacting with CD28, and a number of additional costimulatory molecules have recently been identified, including members of the tumor necrosis family. The positive signals induced by these molecules are counterbalanced by other members of the costimulatory family, including cytotoxic T lymphocyte-associated antigen (CTLA)-4, programmed death (PD)-1, and B and T lymphocyte attenuator (BTLA), which dampen immune responses. In this review, we describe the fundamental properties of costimulatory molecules and address the influence of costimulatory signals on allergic responses.