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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)136-150.e6
JournalImmunity
Volume52
Issue number1
DOIs
StatePublished - Jan 14 2020
Externally publishedYes

Keywords

  • CD8 T cells
  • FcgRIIB
  • Fgl2
  • apoptosis
  • transplantation
  • tumor immunology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Signaling through the Inhibitory Fc Receptor FcγRIIB Induces CD8<sup>+</sup> T Cell Apoptosis to Limit T Cell Immunity'. Together they form a unique fingerprint.

Cite this