| First Author | Ronchetti S | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 9 | Pages | 5916-26 |
| PubMed ID | 17947665 | Mgi Jnum | J:153004 |
| Mgi Id | MGI:4360592 | Doi | 10.4049/jimmunol.179.9.5916 |
| Citation | Ronchetti S, et al. (2007) Glucocorticoid-induced TNFR-related protein lowers the threshold of CD28 costimulation in CD8+ T cells. J Immunol 179(9):5916-26 |
| abstractText | 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. |
