Send to

Choose Destination
J Autoimmun. 2019 Mar;98:86-94. doi: 10.1016/j.jaut.2018.12.002. Epub 2019 Jan 5.

Multi-faceted inhibition of dendritic cell function by CD4+Foxp3+ regulatory T cells.

Author information

Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Electronic address:


CTLA-4 is required for CD4+Foxp3+ regulatory T (Treg) cell function, but its mode of action remains incompletely defined. Herein we generated Ctla-4ex2fl/flFoxp3-Cre mice with Treg cells exclusively expressing a naturally occurring, ligand-independent isoform of CTLA-4 (liCTLA-4) that cannot interact with the costimulatory molecules CD80 and CD86. The mice did not exhibit any signs of effector T cell activation early in life, however, at 6 months of age they exhibited excessive T cell activation and inflammation in lungs. In contrast, mice with Treg cells completely lacking CTLA-4 developed lymphoproliferative disease characterized by multi-organ inflammation early in life. In vitro, Treg cells exclusively expressing liCTLA-4 inhibited CD80 and CD86 expression on dendritic cells (DC). Conversely, Treg cells required the extra-cellular part of CTLA-4 to up-regulate expression of the co-inhibitory molecule PD-L2 on DCs. Transcriptomic analysis of suppressed DCs revealed that Treg cells induced a specific immunosuppressive program in DCs.


CTLA-4; Costimulation; Dendritic cells; PD-L2; Regulatory T cells


Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center