| First Author | Yeo CJ | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 1 | Pages | 60-6 |
| PubMed ID | 21182077 | Mgi Jnum | J:174660 |
| Mgi Id | MGI:5140291 | Doi | 10.1002/eji.201040873 |
| Citation | Yeo CJ, et al. (2011) T-bet-mediated differentiation of the activated CD8+ T cell. Eur J Immunol 41(1):60-6 |
| abstractText | The T-box transcription factor, T-bet promotes the differentiation of short-lived effector CD8(+) T cells at the expense of central memory cells. How T-bet mediates these effects, and whether they are directly caused by T-bet alone are unknown, because expression of T-bet requires stimulation of the T cell by inflammatory and growth cytokines, which may have T-bet-independent functions involving T-cell differentiation. We developed an in vitro system of ectopic T-bet expression that avoids the effects of inflammatory cytokines to determine which aspects of the T-bet phenotype may be accounted for by T-bet alone. Ectopic T-bet expression by OT-I CD8(+) T cells stimulated by the H2-Kb (SIINFEKL) complex and cultured with 2 ng/mL IL-2 induced a coordinated change in gene expression leading to down-regulation of CD127 and SOCS-1 and up-regulation of CD122 and IL-15 receptor alpha, switching the cellular survival cytokine from IL-7 to IL-15. T-bet expression and 2 ng/mL IL-2 also led to a capacity for IFN-gamma and Fas ligand expression, confirming a role in eliciting these effector functions. Finally, ectopic T-bet promoted the expression of B lymphocyte-induced maturation protein 1 by OT-I cells in the presence of 20 ng/mL IL-2, providing a mechanism for the role of T-bet in driving terminal differentiation in concert with a high level of IL-2 receptor signalling. |
