| First Author | Clavijo PE | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 3 | Pages | 1213-21 |
| PubMed ID | 22205033 | Mgi Jnum | J:180752 |
| Mgi Id | MGI:5307176 | Doi | 10.4049/jimmunol.1100793 |
| Citation | Clavijo PE, et al. (2012) Anergic CD8+ T lymphocytes have impaired NF-kappaB activation with defects in p65 phosphorylation and acetylation. J Immunol 188(3):1213-21 |
| abstractText | Because of the cytotoxic potential of CD8(+) T cells, maintenance of CD8(+) peripheral tolerance is extremely important. A major peripheral tolerance mechanism is the induction of anergy, a refractory state in which proliferation and IL-2 production are inhibited. We used a TCR transgenic mouse model to investigate the signaling defects in CD8(+) T cells rendered anergic in vivo. In addition to a previously reported alteration in calcium/NFAT signaling, we also found a defect in NF-kappaB-mediated gene transcription. This was not due to blockade of early NF-kappaB activation events, including IkappaB degradation and NF-kappaB nuclear translocation, as these occurred normally in tolerant T cells. However, we discovered that anergic cells failed to phosphorylate the NF-kappaB p65 subunit at Ser(311) and also failed to acetylate p65 at Lys(310). Both of these modifications have been implicated as critical for NF-kappaB transactivation capacity, and thus, our results suggest that defects in key phosphorylation and acetylation events are important for the inhibition of NF-kappaB activity (and subsequent T cell function) in anergic CD8(+) T cells. |
