| First Author | Zhang EY | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 8 | Pages | 4579-89 |
| PubMed ID | 21411729 | Mgi Jnum | J:172518 |
| Mgi Id | MGI:5008207 | Doi | 10.4049/jimmunol.1001604 |
| Citation | Zhang EY, et al. (2011) Gads regulates the expansion phase of CD8+ T cell-mediated immunity. J Immunol 186(8):4579-89 |
| abstractText | The Gads adaptor protein is critical for TCR-mediated Ca(2+) mobilization. We investigated the effect of Gads deficiency on the proliferation of CD8(+) T cells following peptide stimulation and in the context of infection with an intracellular pathogen. We stimulated CD8(+) T cells from Gads(+/+) OT-I and Gads(-/-) OT-I mice with cognate Ag (SIINFEKL) or altered peptide ligand. In vitro experiments revealed that Gads was required for optimal proliferation of CD8(+) T cells. This defect was most evident at the early time points of proliferation and when low doses of Ag were used as stimuli. Cell cycle analysis demonstrated that Gads(-/-) CD8(+) T cells had impaired TCR-mediated exit from the G(0) phase of the cell cycle. Furthermore, Gads(-/-) CD8(+) T cells had delayed expression of c-myc and CD69 upon the stimulation with SIINFEKL. We then investigated how Gads deficiency would impact CD8(+) T cell-mediated immunity in the context of infection with an intracellular pathogen. At early time points, Gads(+/+) and Gads(-/-) CD8(+) T cells proliferated to a similar extent, despite the fact that expression of CD69 and CD25 was reduced in the absence of Gads. After 5 d postinfection, Gads was required to sustain the expansion phase of the immune response; the peak response of Gads(-/-) cells was significantly lower than for Gads(+/+) cells. However, Gads was not required for the differentiation of naive CD8(+) T cells into memory cells. We conclude that the primary function of Gads is to regulate the sensitivity of the TCR to Ag ligation. |
