| First Author | Gelman AE | Year | 2006 |
| Journal | Immunity | Volume | 25 |
| Issue | 5 | Pages | 783-93 |
| PubMed ID | 17055754 | Mgi Jnum | J:116106 |
| Mgi Id | MGI:3692854 | Doi | 10.1016/j.immuni.2006.08.023 |
| Citation | Gelman AE, et al. (2006) The adaptor molecule MyD88 activates PI-3 kinase signaling in CD4+ T cells and enables CpG oligodeoxynucleotide-mediated costimulation. Immunity 25(5):783-93 |
| abstractText | While T cells respond directly to toll-like receptor (TLR) agonists, TLR-signaling pathways in T cells are poorly characterized. Here we demonstrate in CD4(+) T cells that CpG DNA directly enhances proliferation, prevents anergy, and augments humoral responses to a T cell-dependent antigen by a Myeloid differentiation primary-response protein 88 (MyD88) and Phosphatidylinositol 3-kinase (PI-3 kinase)-dependent pathway. PI-3 kinase activation required a putative Src-homology domain (SH2) binding motif in the MyD88 Toll-Like or IL-1 Receptor (TIR) domain. Reconstitution of MyD88-deficient primary T cells with a MyD88 transgene mutated in this motif abrogated association of PI-3 kinase with MyD88, phosphorylation of protein kinase B (Akt) and Glycogen Synthetase Kinase-3 (GSK-3), and interleukin-2 (IL-2) production. The MyD88 death domain, on the other hand, was required for NF-kB activation and survival. These studies identify a MyD88-dependent PI-3 kinase-signaling pathway in T cells that differentiates CpG DNA-mediated proliferation from survival and is required for an in vivo T cell-dependent immune response. |
