Co-stimulation and co-inhibition are two types of regulatory signals that modulate T cell activation and function. Co-stimulation is a positive regulatory signal that is required for full T cell activation, while co-inhibition is a negative regulatory signal that inhibits T cell activation.
Co-stimulation: Co-stimulatory signals are provided by antigen-presenting cells (APCs) and are required in addition to antigen recognition by the T cell receptor (TCR) for full T cell activation. Co-stimulatory molecules, such as CD80 and CD86, are expressed on the surface of APCs and interact with co-stimulatory receptors, such as CD28, on T cells. This interaction provides a critical second signal that enhances TCR signaling and promotes T cell activation, proliferation, and differentiation.
Co-inhibition: Co-inhibitory signals are negative regulatory signals that inhibit T cell activation and limit immune responses. Co-inhibitory molecules, such as programmed death-1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), are expressed on the surface of T cells and interact with their ligands, PD-L1/PD-L2 and CD80/CD86, respectively, expressed on APCs. This interaction downregulates T cell activation, proliferation, and cytokine production, thereby dampening the immune response and preventing excessive inflammation.
The balance between co-stimulatory and co-inhibitory signals is critical for the regulation of T cell activation and tolerance. Dysregulation of co-stimulation or co-inhibition can result in immune dysfunction, autoimmunity, or immunodeficiency. Therapeutic manipulation of co-stimulatory and co-inhibitory pathways has emerged as a promising approach for the treatment of autoimmune diseases, cancer, and infectious diseases.