Prevention of chronic graft-versus-host disease by stimulation with glucocorticoid-induced TNF receptor

Glucocorticoid-induced Tumor Necrosis Factor Receptor Negatively Regulates Activation of Human Primary Natural Killer (NK) Cells by Blocking Proliferative Signals and Increasing NK Cell Apoptosis

“…Therefore, GITR-GITRL interactions are thought to potentiate T cell activation and function (14,15,(41)(42)(43). Consistent with the co-stimulatory role of GITR for T cells and T cell immune responses, a series of studies has shown that manipulation of the GITR-GITRL interaction can be an effective strategy for immunotherapies for tumors, viral infections, and autoimmune diseases (22)(23)(24)(25)(26)(27)(28)(29)(30). Recent studies have suggested that GITR is also expressed in the innate immune system and can modulate the functions of innate immune response (13,17).…”

“…It is expressed on macrophages, B cells (8,13,(15)(16)(17), and NK cells (18,19), whereas its cognate ligand (GITRL) is constitutively expressed on antigenpresenting cells, such as dendritic cells and B cells (20,21). Manipulation of the GITR-GITRL interaction is suggested as a target for tumor immunotherapy, treatment of viral infection, and treatment of autoimmune diseases (22)(23)(24)(25)(26)(27)(28)(29)(30). This possibility has intensified the significance of studying GITR-GITRL interactions.…”

Maintenance of CD8+T-cell anergy by CD4+CD25+ regulatory T cells in chronic graft-versus-host disease

“…We induced cGVHD by transferring total or Treg cell-depleted DBA/2 spleen/lymph node cells into unirradiated BDF1 mice. Three weeks after disease induction, we measured levels of anti-DNA IgG1 autoantibody, a predominant immunoglobulin isotype in cGVHD (Kim et al, 2005;2006b). Introduction of Treg cell-depleted parental cells induced significantly lower levels of anti-DNA IgG1 in the recipient than did introduction of total parental cells (Figure 1).…”

Glucocorticoid‐Induced TNFR‐Related (GITR) Protein and Its Ligand in Antitumor Immunity: Functional Role and Therapeutic Modulation

“…Two groups reported on the effect of agonistic anti-GITR antibody in models of graft versus host disease (GvHD). Kim and coworkers reported that GITR stimulation converted chronic to active GvHD, ameliorated disease symptoms, and affected survival in (C57BL/6xDBA/2)F 1 mice with chronic GvHD upon transfer of DBA/2 parental cells, and this was due to modulation of effector T cells [20, 64]. Muriglan et al found that GITR stimulation enhanced alloreactive CD8+ T cell proliferation and function, but decreased reactivity of alloreactive CD4+ T cells.…”