CTL-Promoting Effects of IL-21 Counteract Murine Lupus in the Parent→F1 Graft-versus-Host Disease Model

The Journal of Immunology : Official Journal of the American Association of Immunologists
Vinh NguyenV Rus

Abstract

IL-21 promotes B cell and CTL responses in vivo, conferring IL-21 with a role in both humoral and cellular responses. Because CTL can target and eliminate autoreactive B cells, we investigated whether IL-21R signaling in CD8 T cells would alter the expansion of autoreactive B cells in an autoimmune setting. We addressed this question using the parent→F1 murine model of acute and chronic (lupus-like) graft-versus-host disease (GVHD) as models of a CTL-mediated or T-dependent B cell-mediated response, respectively. Induction of acute GVHD using IL-21R-deficient donor T cells resulted in decreased peak donor CD8 T cell numbers and decreased CTL effector function due to impaired granzyme B/perforin and Fas/Fas ligand pathways and a phenotype of low-intensity chronic GVHD with persistent host B cells, autoantibody production, and mild lupus-like renal disease. CTL effector maturation was critically dependent on IL-21R signaling in Ag-specific donor CD8, but not CD4, T cells. Conversely, treatment of DBA/2J→F1 chronic GVHD mice with IL-21 strongly promoted donor CD8 T cell expansion and rescued defective donor anti-host CTLs, resulting in host B cell elimination, decreased autoantibody levels, and attenuated renal disease, despite ev...Continue Reading

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Citations

May 26, 2017·Current Opinion in Rheumatology·Wei LiLaurence Morel
Mar 31, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Violeta RusHorea G Rus
Feb 19, 2019·Journal of Autoimmunity·Di LongQianjin Lu
Mar 16, 2021·American Journal of Physiology. Renal Physiology·Jung Nam AnSeung Hee Yang
Jul 6, 2021·Journal of Autoimmunity·Heather M RenNancy J Olsen
Jun 30, 2021·Current Opinion in Rheumatology·Ping-Min Chen, George C Tsokos

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