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Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2007

AutorInnen: Ronchetti, S; Nocentini, G; Bianchini, R; Krausz, LT; Migliorati, G; Riccardi, C

Titel: Glucocorticoid-induced TNFR-related protein lowers the threshold of CD28 costimulation in CD8+ T cells.

Quelle: J Immunol. 2007; 179(9):5916-26

Autor/innen der Vetmeduni Vienna:

Bianchini Rodolfo

Diese Publikation wurde nicht im Namen der Vetmeduni Vienna erstellt und ist deshalb ausschließlich der persönlichen Publikationsliste des/der Autors/Autorin zugeordnet!

CD28 is well characterized as a costimulatory molecule in T cell activation. Recent evidences indicate that TNFR superfamily members, including glucocorticoid-induced TNFR-related protein (GITR), act as costimulatory molecules. In this study, the relationship between GITR and CD28 has been investigated in murine CD8(+) T cells. When suboptimal doses of anti-CD3 Ab were used, the absence of GITR lowered CD28-induced activation in these cells whereas the lack of CD28 did not affect the response of CD8(+) T cells to GITR costimulus. In fact, costimulation of CD28 in anti-CD3-activated GITR(-/-) CD8(+) T cells resulted in an impaired increase of proliferation, impaired protection from apoptosis, and an impaired rise of activation molecules such as IL-2R, IL-2, and IFN-gamma. Most notably, CD28-costimulated GITR(-/-) CD8(+) T cells revealed lower NF-kappaB activation. As a consequence, up-regulation of Bcl-x(L), one of the major target proteins of CD28-dependent NF-kappaB activation, was defective in costimulated GITR(-/-) CD8(+) T cells. What contributed to the response to CD28 ligation in CD8(+) T cells was the early up-regulation of GITR ligand on the same cells, the effect of which was blocked by the addition of a recombinant GITR-Fc protein. Our results indicate that GITR influences CD8(+) T cell response to CD28 costimulation, lowering the threshold of CD8(+) T cell activation.

Keywords Pubmed: Animals
CD28 Antigensgeneticsimmunologymetabolism
CD8-Positive T-Lymphocytesimmunologymetabolism
Cell Proliferation
Cells, Cultured
Glucocorticoid-Induced TNFR-Related Protein
Lymphocyte Activationimmunology
Mice, Knockout
NF-kappa Bmetabolism
Receptors, Nerve Growth Factordeficiencygeneticsmetabolism
Receptors, Tumor Necrosis Factordeficiencygeneticsmetabolism
Signal Transduction
bcl-X Proteinmetabolism

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