2004
DOI: 10.4049/jimmunol.172.10.5823
|View full text |Cite
|
Sign up to set email alerts
|

Cutting Edge: The Natural Ligand for Glucocorticoid-Induced TNF Receptor-Related Protein Abrogates Regulatory T Cell Suppression

Abstract: CD4+25+ regulatory T (Treg) cells maintain immunological self-tolerance through mechanisms that are only in part understood. Previous studies suggest that the glucocorticoid-induced TNFR-related protein (GITR), which is preferentially expressed on the surface of Treg cells, potentially provides a signal that abrogates Treg suppression. In this study, we show that a soluble form of mouse GITR ligand (sGITR-L) induces GITR-dependent NF-κB activation and blocks in vitro suppression mediated by both resting and pr… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

9
165
1

Year Published

2005
2005
2017
2017

Publication Types

Select...
7
2

Relationship

0
9

Authors

Journals

citations
Cited by 182 publications
(175 citation statements)
references
References 13 publications
9
165
1
Order By: Relevance
“…Treg can interact with other immune populations via soluble factors and/or via cell-contactdependent mechanisms. Whereas in vivo studies have suggested a major role for soluble factors, such as IL-10 [41], TGF-b [42], or IL-35 [43], most in vitro experiments described a cell-contactdependent mechanism, involving CTLA-4 [44,45], GITR [46], Perforin [33], or Granzyme B [34]. Our data suggest that Perforin/ Granzyme-induced apoptosis does not play a major role in Tregmediated suppression of mouse gd-T-cell activity.…”
Section: Discussionmentioning
confidence: 51%
See 1 more Smart Citation
“…Treg can interact with other immune populations via soluble factors and/or via cell-contactdependent mechanisms. Whereas in vivo studies have suggested a major role for soluble factors, such as IL-10 [41], TGF-b [42], or IL-35 [43], most in vitro experiments described a cell-contactdependent mechanism, involving CTLA-4 [44,45], GITR [46], Perforin [33], or Granzyme B [34]. Our data suggest that Perforin/ Granzyme-induced apoptosis does not play a major role in Tregmediated suppression of mouse gd-T-cell activity.…”
Section: Discussionmentioning
confidence: 51%
“…The administration of a-GITR mAb was previously shown to induce autoimmune manifestations in mice [48], and to abrogate Treg-mediated suppression of Teff activity in vitro [47,48]. This was possibly due to GITR triggering rather than blocking, as the effect of the antibody was mimicked by GITR-L fusion proteins [46,50]. However, cross-linking of GITR was later shown to co-stimulate both Treg and Teff [50][51][52].…”
Section: Discussionmentioning
confidence: 99%
“…Several TNFR family members have costimulatory effects on T cells, including CD27, 4-1BB (CD137), OX40 (CD134), CD30 and GITR, and GITR and OX40 are also implicated in control of Treg function (19 -23). GITR is expressed at high levels on CD4 ϩ CD25 ϩ Tregs and its ligation by GITR ligand expressed by APC revokes Treg suppression and provides a costimulatory signal for Ag-driven proliferation of naive T cells and polarized Th1 and Th2 clones (22,23). Likewise, although both naive and activated Tregs express OX40, triggering OX40 on Tregs using agonist Abs inhibited their capacity to suppress, and restored Teff cell proliferation and IL-2 cytokine production (24).…”
Section: Discussionmentioning
confidence: 99%
“…GITR is also inducible on naïve CD4 + T cells activated via the TCR. When engaged by its ligand, GITR-L; GITR triggers NF-κB activation and prevents in vitro suppression mediated by T reg cells by enhancing IL-2 secretion by the responder T cells (36). We tested if the increased suppressive ability of T reg cells is due to increased GITR expression and is GITR dependent.…”
Section: Suppressive Effects Of Cd4 + Cd25 + T Reg Cells From Cd5 −/−mentioning
confidence: 99%