Journal Article

Antiapoptotic function of NF-κB in T lymphocytes is influenced by their differentiation status: roles of Fas, c-FLIP, and Bcl-xL

Goenka, S, Ballard, D W, Corn, R A, Stanic, A K, Mora, A L, Aronica, M, Boothby, M, Stanley, S, Joyce, S

2003

Overview

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- κ B/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- κ B/Rel signaling to investigate the role of this pathway in proliferation and death of mature T cells in vivo . The results indicate that NF- κ B 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- κ B 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- κ B 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- κ B 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- κ B in T lymphoid homeostasis in vivo , but this effect and its underlying mechanisms are influenced by the developmental state of the lymphocyte.

• Publisher: Nature Publishing Group UK
• Subject: Apoptosis / Biochemistry / Biomedical and Life Sciences / Cell Biology / Cell Cycle Analysis / Life Sciences / original-paper / Stem Cells