Signaling through the Inhibitory Fc Receptor FcγRIIB Induces CD8 T Cell Apoptosis to Limit T Cell Immunity.

Effector CD8 T cells are important mediators of adaptive immunity, and receptor-ligand interactions that regulate their survival may have therapeutic potential. Here, we identified a subset of effector CD8 T cells that expressed the inhibitory fragment crystallizable (Fc) receptor FcγRIIB following activation and multiple rounds of division. CD8 T cell-intrinsic genetic deletion of Fcgr2b increased CD8 effector T cell accumulation, resulting in accelerated graft rejection and decreased tumor volume in mouse models.

Influence of T Cell Coinhibitory Molecules on CD8 Recall Responses.

T cell co-signaling molecules play an important role in fine-tuning the strength of T cell activation during many types of immune responses, including infection, cancer, transplant rejection, and autoimmunity. Over the last few decades, intense research into these cosignaling molecules has provided rich evidence to suggest that cosignaling molecules may be harnessed for the treatment of immune-related diseases. In particular, coinhibitory molecules such as programmed-death 1, 2B4, BTLA, TIGIT, LAG-3, TIM-3, and CTLA-4 inhibit T cell responses by counteracting TCR and costimulatory signals, leading to the inhibition of proliferation and effector function and the downregulation of activation and adhesion molecules at the cell surface.