| First Author | Whitman E | Year | 2015 |
| Journal | Mol Immunol | Volume | 63 |
| Issue | 2 | Pages | 268-78 |
| PubMed ID | 25089028 | Mgi Jnum | J:222337 |
| Mgi Id | MGI:5644378 | Doi | 10.1016/j.molimm.2014.07.015 |
| Citation | Whitman E, et al. (2015) NKG2D receptor activation of NF-kappaB enhances inflammatory cytokine production in murine effector CD8(+) T cells. Mol Immunol 63(2):268-78 |
| abstractText | To induce strong immune responses, naive CD8(+) T cells require stimulation through the TCR and costimulatory receptors. However, the biological effect of activating costimulatory receptors on effector T cells is still unclear. One costimulatory receptor that is likely to be engaged at the target site is NKG2D. This activating receptor is expressed on human and murine CD8(+) T cells with its ligands expressed on the majority of tumor cells and during some infections. In order to determine how activation of costimulatory receptors alters effector CD8(+) T cell functions, this study compared the activation of the NF-kappaB signaling pathway by two costimulatory receptors, CD28 and NKG2D. Compared to CD28 costimulation, activation of murine effector CD8(+) T cells through CD3 and NKG2D receptors enhanced activation of NF-kappaB as shown by increased phosphorylation of IKKalpha, IkappaBalpha, and NF-kappaB and IkappaBalpha degradation. NKG2D costimulation also increased activation, nuclear translocation, and DNA binding of NF-kappaB p65/p50 dimers. Activation of the NF-kappaB pathway also lead to increased gene expression and secretion of pro-inflammatory cytokines, including IFNalpha and IFNgamma, and decreased gene expression and secretion of anti-inflammatory cytokines, including IL-10 and CCL2. Altered NF-kappaB activation also increased expression of the effector molecules TNFalpha, lymphotoxins alpha and beta, and Fas ligand, and increased tumor cell killing through FasL. These data show that compared to CD28 costimulation, activation through the NKG2D receptor leads to the differential activation of the NF-kappaB signaling pathway and potentially enhances the anti-tumor and anti-viral functions of effector CD8(+) T cells. |
