| First Author | Nurieva R | Year | 2006 |
| Journal | EMBO J | Volume | 25 |
| Issue | 11 | Pages | 2623-33 |
| PubMed ID | 16724117 | Mgi Jnum | J:109521 |
| Mgi Id | MGI:3629240 | Doi | 10.1038/sj.emboj.7601146 |
| Citation | Nurieva R, et al. (2006) T-cell tolerance or function is determined by combinatorial costimulatory signals. EMBO J 25(11):2623-33 |
| abstractText | Activated in immune responses, T lymphocytes differentiate into effector cells with potent immune function. CD28 is the most prominent costimulatory receptor for T-cell activation. However, absence of CD28 costimulation did not completely impair effector function of CD4 or CD8 T cells. Moreover, increasing number of costimulatory molecules are recently found on antigen-presenting cells to regulate T-cell activation. To understand the molecular mechanisms that determine T-cell function or tolerance, we have collectively examined the roles of positive and negative costimulatory molecules. Antigen-specific naive CD4 and CD8 T cells, only when activated in the absence of both CD28 and ICOS pathways, were completely impaired in effector function. These tolerant T cells not only were anergic with profound defects in TcR signal transduction but also completely lacked expression of effector-specific transcription factors. T-cell tolerance induction in this system requires the action by negative costimulatory molecules; T-cell proliferation and function was partially restored by inhibiting PD-1, B7-H3 or B7S1. This work demonstrates that T-cell function or tolerance is controlled by costimulatory signals. |
