costimulatoire

Costimulatoire, or costimulatory signaling, refers to the set of secondary signals required for full activation of adaptive immune responses. In T cells, activation typically requires two signals: signal 1 from the T cell receptor recognizing peptide-MHC complexes, and signal 2 from costimulatory receptors engaged by ligands on antigen-presenting cells. Absence of costimulation often leads to anergy, deletion, or failure to differentiate, contributing to peripheral tolerance.

The best-characterized costimulatory axis is the B7 family on antigen-presenting cells (CD80/CD86) engaging CD28 on T cells. This signal promotes interleukin-2 production, clonal expansion, and differentiation. CTLA-4 provides a negative regulator that outcompetes CD28 and dampens activation; CTLA-4–Ig fusion proteins (abatacept, belatacept) are used to dampen immune responses in autoimmunity and transplantation.

Beyond CD28, several other costimulatory and coinhibitory pathways modulate T cell responses. ICOS-ICOSL, OX40-OX40L, 4-1BB (CD137), and CD27-CD70 can enhance activation and memory formation under appropriate conditions. CD40-CD40L interactions between T cells and B cells or dendritic cells support B cell help and dendritic cell maturation. The PD-1/PD-L1 axis serves as a dominant inhibitory pathway that reduces costimulatory signaling during chronic antigen exposure.

Clinical relevance is wide: proper costimulation shapes immunity and tolerance; dysregulation can contribute to autoimmunity or insufficient anti-tumor responses. Therapeutically, modulation of costimulatory signals underpins cancer immunotherapy with checkpoint inhibitors (e.g., CTLA-4 or PD-1 blockade) to boost T cell activity, as well as strategies to induce tolerance in transplantation or autoimmune diseases using CTLA-4–Ig or related approaches.