| First Author | Beisner DR | Year | 2003 |
| Journal | J Immunol | Volume | 171 |
| Issue | 1 | Pages | 247-56 |
| PubMed ID | 12817005 | Mgi Jnum | J:132831 |
| Mgi Id | MGI:3777029 | Doi | 10.4049/jimmunol.171.1.247 |
| Citation | Beisner DR, et al. (2003) The requirements for Fas-associated death domain signaling in mature T cell activation and survival. J Immunol 171(1):247-56 |
| abstractText | Fas-associated death domain (FADD) is a death domain containing cytoplasmic adapter molecule required for the induction of apoptosis by death receptors. Paradoxically, FADD also plays a crucial role in the development and proliferation of T cells. Using T cells from mice expressing a dominant negative form of FADD (FADDdd), activation with anti-TCR Ab and costimulation or exogenous cytokines is profoundly diminished. This is also seen in wild-type primary T cells transduced with the same transgene, demonstrating that FADD signaling is required in normally differentiated T cells. The defective proliferation does not appear to be related to the early events associated with TCR stimulation. Rather, with a block in FADD signaling, stimulated T cells exhibit a high rate of cell death corresponding to the initiation of cell division. Although CD4 T cells exhibit a moderate deficiency, this effect is most profound in CD8 T cells. In vivo, the extent of this defective accumulation is most apparent; lymphocytic choriomenigitis virus-infected FADDdd-expressing mice completely fail to mount an Ag-specific response. These results show that, in a highly regulated fashion, FADD, and most likely caspases, can transduce either a signal for survival or one that leads directly to apoptosis and that the balance between these opposing outcomes is crucial to adaptive immunity. |
