[PDF][PDF] Signaling through the inhibitory Fc receptor FcγRIIB induces CD8+ T cell apoptosis to limit T cell immunity

AB Morris, CR Farley, DF Pinelli, LE Adams, MS Cragg… - Immunity, 2020 - cell.com
AB Morris, CR Farley, DF Pinelli, LE Adams, MS Cragg, JM Boss, CD Scharer, M Fribourg
Immunity, 2020cell.com
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 …
Summary
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.
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