cellcostimulation

Cell costimulation refers to the signals provided by antigen-presenting cells (APCs) to T cells that are crucial for a full and effective T cell activation. While the initial recognition of an antigen by the T cell receptor (TCR) provides the first signal, costimulatory signals are considered the second signal, without which T cell activation can be abortive, lead to tolerance, or result in T cell anergy (a state of unresponsiveness).

Key costimulatory molecules are expressed on the surface of APCs, such as dendritic cells and macrophages, and bind to their corresponding receptors on T cells. The most well-characterized costimulatory pathway involves the interaction between CD28 on the T cell and B7 family molecules (CD80 and CD86) on the APC. This CD28-B7 interaction is essential for T cell proliferation, cytokine production, and survival.

Other important costimulatory molecules include members of the tumor necrosis factor (TNF) receptor superfamily on T cells, such as OX40, 4-1BB, and ICOS, which interact with their ligands on APCs to further enhance T cell responses, particularly for effector and memory T cell development. Conversely, inhibitory molecules like CTLA-4 and PD-1, also expressed on T cells, can bind to ligands on APCs and suppress T cell activation, playing a critical role in maintaining immune homeostasis and preventing autoimmunity. The balance between costimulatory and coinhibitory signals dictates the outcome of T cell activation, influencing whether an immune response is mounted, sustained, or dampened.