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Immunity. 2020 Jan 14;52(1):136-150.e6. doi: 10.1016/j.immuni.2019.12.006.

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

Author information

1
Department of Surgery, Emory University, Atlanta, GA, USA.
2
Antibody and Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
3
Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
4
Translational Transplant Research Center and the Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
5
Department of Surgery, Emory University, Atlanta, GA, USA. Electronic address: mandy.ford@emory.edu.

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.

KEYWORDS:

CD8(+) T cells; FcgRIIB; Fgl2; apoptosis; transplantation; tumor immunology

PMID:
31940267
DOI:
10.1016/j.immuni.2019.12.006
[Indexed for MEDLINE]

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