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. Immunoglobulin G (IgG) antibody was not required for FcγRIIB-mediated control of CD8⁺ T cell immunity, and instead, the immunosuppressive cytokine fibrinogen-like 2 (Fgl2) was a functional ligand for FcγRIIB on CD8⁺ T cells. Fgl2 induced caspase-3/7-mediated apoptosis in Fcgr2b⁺, but not Fcgr2b^-/-, CD8⁺ T cells. Increased expression of FcγRIIB correlated with freedom from rejection following withdrawal from immunosuppression in a clinical trial of kidney transplant recipients. Together, these findings demonstrate a cell-intrinsic coinhibitory function of FcγRIIB in regulating CD8⁺ T cell immunity. Copyright © 2019. Published by Elsevier Inc.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}