CD28 costimulatory pathway (CD28 pathway)

The CD28 costimulatory pathway is a critical signaling axis in the adaptive immune system, providing the 'second signal' necessary for the full activation of T lymphocytes [7, 9]. This pathway is initiated when the CD28 receptor, constitutively expressed on T cells, binds to its ligands CD80 (B7-1) or CD86 (B7-2) on the surface of professional antigen-presenting cells [9, 11]. This interaction works in tandem with T-cell receptor (TCR) signaling to promote T-cell proliferation, survival, and the production of key cytokines such as interleukin-2 (IL-2) [7, 11]. Dysregulation of this pathway is central to the pathogenesis of various autoimmune disorders and the rejection of transplanted organs, where excessive T-cell activity causes host tissue damage [6, 8]. Consequently, therapeutic agents like Abatacept and Belatacept have been developed to block this interaction and induce immune tolerance [3, 6]. In the context of cancer, the pathway is often suppressed by the inhibitory receptor CTLA-4, which competes for the same ligands; thus, checkpoint inhibitors targeting CTLA-4 aim to restore CD28-mediated costimulation to enhance anti-tumor immunity [5, 14].

Other names

CD80/CD86-mediated CD28 costimulatory pathwayB7-CD28 pathwayT-cell costimulatory pathwaySignal 2 pathwayCD28-B7 interaction

Modulation of T-cell activation by blocking or stimulating the interaction between the CD28 receptor and its ligands CD80 and CD86.