| First Author | Müller S | Year | 2009 |
| Journal | Eur J Immunol | Volume | 39 |
| Issue | 11 | Pages | 3171-80 |
| PubMed ID | 19681056 | Mgi Jnum | J:154204 |
| Mgi Id | MGI:4367413 | Doi | 10.1002/eji.200939554 |
| Citation | Muller S, et al. (2009) Soluble TNF-alpha but not transmembrane TNF-alpha sensitizes T cells for enhanced activation-induced cell death. Eur J Immunol 39(11):3171-3180 |
| abstractText | In addition to its proinflammatory effects, TNF-alpha exhibits immunosuppression. Here, we compared the capacities of transmembrane TNF-alpha (tmTNF) and soluble TNF-alpha (sTNF) in regulating expansion of activated T cells by apoptosis. Splenic CD4(+) T cells from wtTNF, TNF-alpha-deficient (TNF(-/-)) and TNF(-/-) mice expressing a non-cleavable mutant tmTNF showed comparable proliferation rates upon TCR-mediated stimulation. Activation-induced cell death (AICD), however, was significantly attenuated in tmTNF and TNF(-/-), compared with wtTNF CD4(+) T cells. Addition of sTNF during initial priming was sufficient to enhance susceptibility to AICD in tmTNF and TNF(-/-) CD4(+) T cells to levels seen in wtTNF CD4(+) T cells, whereas addition of sTNF only during restimulation failed to enhance AICD. sTNF-induced, enhanced susceptibility to AICD was dependent on both TNF receptors. The reduced susceptibility of tmTNF CD4(+) T cells for AICD was also evident in an in vivo model of adoptively transferred CD4(+) T-cell-mediated colonic inflammation. Hence, the presence of sTNF during T-cell priming may represent an important mechanism to sensitize activated T cells for apoptosis, thereby attenuating the extent and duration of T-cell reactivities and subsequent T-cell-mediated, excessive inflammation. |
