| First Author | Nurieva RI | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 2 | Pages | 1096-103 |
| PubMed ID | 17617602 | Mgi Jnum | J:149397 |
| Mgi Id | MGI:3848408 | Doi | 10.4049/jimmunol.179.2.1096 |
| Citation | Nurieva RI, et al. (2007) A costimulation-initiated signaling pathway regulates NFATc1 transcription in T lymphocytes. J Immunol 179(2):1096-103 |
| abstractText | T cell activation and differentiation is accompanied and mediated by transcriptional reprogramming. The NFATc1 transcription factor is strongly induced upon T cell activation and controls numerous genes involved in the T cell effector function. However, its regulation by physiological stimuli in primary T cells has not been well understood. We previously found that ICOS synergizes with TCR and CD28 to greatly enhance NFATc1 expression in primary T cells. In this study, we have examined the signaling mechanisms whereby costimulation regulates NFATc1 expression. We found that CD28 and ICOS regulate sustained PI3K activity in primary T cells, which is required for NFATc1 up-regulation. CD28 and ICOS costimulation, possibly through Itk, a Tec kinase downstream of the PI3K, enhanced phosphorylation of phospholipase C gamma1 and increased and sustained Ca(2+) flux in T cells. Costimulation of T cells potentiated transcription of the Nfatc1 gene P1 promoter in a PI3K-dependent manner. This work demonstrates an important role for costimulatory receptors in sustaining T cell activation programs leading to Nfatc1 gene transcription and has implications in our understanding of the immune response and tolerance. |
