| First Author | Twu YC | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 2 | Pages | 335-44 |
| PubMed ID | 21268004 | Mgi Jnum | J:175429 |
| Mgi Id | MGI:5285513 | Doi | 10.1002/eji.201040639 |
| Citation | Twu YC, et al. (2011) TNFR1 delivers pro-survival signals that are required for limiting TNFR2-dependent activation-induced cell death (AICD) in CD8+ T cells. Eur J Immunol 41(2):335-44 |
| abstractText | Members of the TNF and TNF receptor (TNFR) superfamily play important roles in the maintenance of homeostasis of the immune system. Furthermore, several members of the TNFR family participate in T-cell activation and sustaining T-cell responses. We have shown that TNFR2 regulates T-cell activation by lowering the activation threshold and providing costimulatory signaling. Furthermore, activated TNFR2(-/-) CD8(+) T cells are highly resistant to activation-induced cell death (AICD). Here, we showed that using anti-TNFR2 antibodies to block TNFR2 on activated WT CD8(+) T cells rendered them resistant to AICD. This resistance of activated TNFR2(-/-) CD8(+) T cells to AICD correlated with the accumulation of TNF receptor-associated factor 2 (TRAF2). Overexpression of TRAF2 by retroviral transfection and knockdown of TRAF2 by small interfering RNA also support this conclusion. Furthermore, neutralizing TNF-alpha reduced TRAF2 accumulation in activated TNFR2(-/-) CD8(+) T cells and increased their susceptibility to AICD. AICD-resistant TNFR2(-/-) CD8(+) T cells expressed elevated levels of phosphorylated IkappaBalpha and higher DNA-binding activity of the p65 NK-kappaB subunit and neutralization of TNF-alpha blocked this increase. Therefore, in activated TNFR2(-/-) CD8(+) T cells, TNFR1 functions as a survival receptor by utilizing high intracellular levels of TRAF2 to promote IkappaBalpha phosphorylation and NF-kappaB activation. |
