| First Author | Morris AB | Year | 2020 |
| Journal | Immunity | Volume | 52 |
| Issue | 1 | Pages | 136-150.e6 |
| PubMed ID | 31940267 | Mgi Jnum | J:290376 |
| Mgi Id | MGI:6431979 | Doi | 10.1016/j.immuni.2019.12.006 |
| Citation | Morris AB, et al. (2020) Signaling through the Inhibitory Fc Receptor FcgammaRIIB Induces CD8(+) T Cell Apoptosis to Limit T Cell Immunity. Immunity 52(1):136-150.e6 |
| abstractText | 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 FcgammaRIIB 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 FcgammaRIIB-mediated control of CD8(+) T cell immunity, and instead, the immunosuppressive cytokine fibrinogen-like 2 (Fgl2) was a functional ligand for FcgammaRIIB on CD8(+) T cells. Fgl2 induced caspase-3/7-mediated apoptosis in Fcgr2b(+), but not Fcgr2b(-/-), CD8(+) T cells. Increased expression of FcgammaRIIB 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 FcgammaRIIB in regulating CD8(+) T cell immunity. |
