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Signaling through the inhibitory Fc receptor Fc gamma RIIB Induces CD8+ T Cell apoptosis to limit T Cell immunity

Signaling through the inhibitory Fc receptor Fc gamma RIIB Induces CD8+ T Cell apoptosis to limit T Cell immunity
Signaling through the inhibitory Fc receptor Fc gamma RIIB 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.
CD8 T cells, FcgRIIB, Fgl2, apoptosis, transplantation, tumor immunology
1097-4180
136-150
Morris, Anna B.
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Farley, Clara R.
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Pinelli, David
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Adams, Layne E.
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Cragg, Mark S.
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Boss, Jeremy M.
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Scharer, Christopher D.
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Fribourg, Miguel
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Cravedi, Paolo
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Heeger, Peter S.
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Ford, Mandy L.
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Morris, Anna B.
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Farley, Clara R.
d441d932-c252-46a0-b5bb-495c29abef18
Pinelli, David
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Adams, Layne E.
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Cragg, Mark S.
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Boss, Jeremy M.
c9cecd2a-b4ec-497e-b877-4ad3c52d295b
Scharer, Christopher D.
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Fribourg, Miguel
d5091362-9c28-47cb-8dee-47365a9e3380
Cravedi, Paolo
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Heeger, Peter S.
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Ford, Mandy L.
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Morris, Anna B., Farley, Clara R., Pinelli, David, Adams, Layne E., Cragg, Mark S., Boss, Jeremy M., Scharer, Christopher D., Fribourg, Miguel, Cravedi, Paolo, Heeger, Peter S. and Ford, Mandy L. (2020) Signaling through the inhibitory Fc receptor Fc gamma RIIB Induces CD8+ T Cell apoptosis to limit T Cell immunity. Immunity, 52 (1), 136-150. (doi:10.1016/j.immuni.2019.12.006).

Record type: Article

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.

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20191211.Cell intrinsic role.FINAL - Accepted Manuscript
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Accepted/In Press date: 12 December 2019
e-pub ahead of print date: 14 January 2020
Published date: 14 January 2020
Keywords: CD8 T cells, FcgRIIB, Fgl2, apoptosis, transplantation, tumor immunology

Identifiers

Local EPrints ID: 437211
URI: http://eprints.soton.ac.uk/id/eprint/437211
ISSN: 1097-4180
PURE UUID: ba1d3c86-2ea0-4292-886d-189062f2d6f5
ORCID for Mark S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X

Catalogue record

Date deposited: 21 Jan 2020 17:37
Last modified: 26 Nov 2021 05:54

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Contributors

Author: Anna B. Morris
Author: Clara R. Farley
Author: David Pinelli
Author: Layne E. Adams
Author: Mark S. Cragg ORCID iD
Author: Jeremy M. Boss
Author: Christopher D. Scharer
Author: Miguel Fribourg
Author: Paolo Cravedi
Author: Peter S. Heeger
Author: Mandy L. Ford

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