Signaling through the Inhibitory Fc Receptor Fc gamma RIIB Induces CD8(+) T Cell Apoptosis to Limit T Cell Immunity

• Type of Material: Article
• Authors: Anna B. Morris, Emory University; Clara R. Farley, Emory University; David F. Pinelli, Emory University; Layne E. Adams, Emory University; Mark S. Cragg, University of Southampton; Jeremy Boss, Emory University; Christopher Scharer, Emory University; Miguel Fribourg, Icahn School of Medicine at Mount Sinai; Paolo Cravedi, Icahn School of Medicine at Mount Sinai; Peter S. Heeger, Icahn School of Medicine at Mount Sinai; Mandy Ford, Emory University
• Language: English
• Date: 2020-01-14
• Publisher: CELL PRESS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: 2020.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.immuni.2019.12.006
• Title of Journal or Parent Work: IMMUNITY
• Volume: 52
• Issue: 1
• Start Page: 136
• End Page: +
• Grant/Funding Information: The study was funded by NIH awards AI073707 and AI104699 to MLF. The CTOT09 trial was supported by NIH (NIAID) U01 AI63594 awarded to PSH.
• Keywords: IGG; RESPONSES; MOUSE; HETEROGENEITY; BIOCONDUCTOR; SHIP; Immunology; DIFFERENTIAL EXPRESSION ANALYSIS; LYMPHOCYTES; Life Sciences & Biomedicine; AID; Science & Technology
• Research Categories: Health Sciences, Immunology; Health Sciences, Public Health

Abstract

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. It is thought that Fc receptors are not expressed on T cells. Morris et al. report that a subset of potent CD8+ effector T cells express and are regulated by the inhibitory Fc receptor FcγRIIB. Ligation of FcγRIIB with the immunosuppressive cytokine Fgl2, rather than IgG, functions to induce caspase-3/7-mediated apoptosis and limit CD8+ T cell immunity.