Cluster of differentiation 28–B7 co-stimulatory axis (CD28–B7 axis) (CD28–B7 axis)

The iNKT cell co-stimulatory axis via the B7–CD28 pathway is a critical signaling mechanism that governs the activation, proliferation, and cytokine production of invariant Natural Killer T (iNKT) cells (UniProt P10747, P33681). While iNKT cells recognize lipid antigens presented by CD1d via their semi-invariant T-cell receptor, full effector function and survival require a secondary signal provided by the interaction of CD28 on the iNKT cell with B7-1 (CD80) or B7-2 (CD86) on antigen-presenting cells (PubMed: 10887109). This axis plays a dual role in immunology: its activation is essential for robust anti-tumor and anti-pathogen responses, while its dysregulation can contribute to autoimmune diseases and allergy (PubMed: 18453589). In the context of cancer immunotherapy, enhancing this pathway can lead to increased secretion of Th1 cytokines like IFN-gamma, which recruits and activates other immune cells. Conversely, therapeutic blockade of this axis using agents like CTLA4-Ig (Abatacept) is employed to treat autoimmune conditions by preventing the co-stimulatory signal necessary for T-cell and iNKT cell activation (FDA: Orencia). Experimental drugs such as anti-CD28 antibodies are also being explored to either stimulate or inhibit this pathway depending on the clinical need, though safety concerns like cytokine release syndrome remain a significant challenge (PubMed: 16929363).

Other names

B7–CD28 pathwayCD28–CD80/CD86 signalingiNKT cell co-stimulationB7-CD28 costimulatory pathway

Modulation of the secondary signal required for iNKT cell activation by targeting the interaction between the CD28 receptor and its B7 ligands (CD80/CD86).