| First Author | Mora AL | Year | 2001 |
| Journal | J Immunol | Volume | 167 |
| Issue | 10 | Pages | 5628-35 |
| PubMed ID | 11698434 | Mgi Jnum | J:135121 |
| Mgi Id | MGI:3790393 | Doi | 10.4049/jimmunol.167.10.5628 |
| Citation | Mora AL, et al. (2001) Inefficient ZAP-70 phosphorylation and decreased thymic selection in vivo result from inhibition of NF-kappaB/Rel. J Immunol 167(10):5628-35 |
| abstractText | Signaling from the TCR regulates T lymphoid survival, deletion by apoptosis, and selective clonal expansion. One set of signaling pathways activated during thymic selection leads to degradation of a cytosolic retention protein, the inhibitor of kappaB (IkappaB)alpha, followed by nuclear translocation of the NF-kappaB/Rel family of transcription factors. It has been found previously that NF-kappaB proteins mediate a pathway signaling the survival of mature T cells and protection of thymocytes against TNF-induced apoptosis. In contrast, we show in this study that a transgenic inhibitor of NF-kappaB/Rel signaling interferes with the negative selection of immature thymocytes by endogenous MHC ligands in vivo. Positive selection of the H-Y TCR also was diminished. This attenuation of thymic selection efficiency was associated with decreased ZAP-70 phosphorylation and TCR signaling of CD69 induction. These findings demonstrate that the NF-kappaB transcriptional pathway plays an important role in normal processes of clonal deletion and they indicate that the NF-kappaB/IkappaB axis can regulate the efficiency of TCR signaling. |
