| First Author | Mora AL | Year | 2003 |
| Journal | Cell Death Differ | Volume | 10 |
| Issue | 9 | Pages | 1032-44 |
| PubMed ID | 12934078 | Mgi Jnum | J:128143 |
| Mgi Id | MGI:3766330 | Doi | 10.1038/sj.cdd.4401257 |
| Citation | Mora AL, et al. (2003) Antiapoptotic function of NF-kappaB in T lymphocytes is influenced by their differentiation status: roles of Fas, c-FLIP, and Bcl-xL. Cell Death Differ 10(9):1032-44 |
| abstractText | Inducible protection from apoptosis in vivo controls the size of cell populations. An important question in this respect is how differentiation affects mechanisms of apoptosis regulation. Among mature T lymphocytes, the NF-kappaB/Rel transcription factors are coupled to receptors that control cell population sizes by concurrently regulating survival and multiplication. In the present study, we used a transgenic inhibitor of NF-kappaB/Rel signaling to investigate the role of this pathway in proliferation and death of mature T cells in vivo. The results indicate that NF-kappaB integrates two critical yet distinct molecular pathways preventing apoptosis affected by the death receptor Fas, coordinately regulating levels of FLIP and Bcl-x(L) in primary T cells. Surprisingly, NF-kappaB blockade preferentially impacted naive as compared to memory T cells. The Fas/FasL pathway was linked to these findings by evidence that the abnormalities imposed by NF-kappaB inhibition were ameliorated by Fas deficiency, particularly for the CD4(+) lineage. Moreover, levels of an inhibitor of Fas-mediated apoptosis, c-FLIP, were diminished in cells expressing the transgenic inhibitor. NF-kappaB was also linked to T cell survival in vivo by mediating induction of Bcl-x(L): restoration of Bcl-x(L) levels reversed the preferential deficit of naive T cells, differentially impacting the CD4 and CD8 subsets. These results show that promoting survival and effective multiplication are central roles for NF-kappaB in T lymphoid homeostasis in vivo, but this effect and its underlying mechanisms are influenced by the developmental state of the lymphocyte. |
