TRANCE (TUMOR-NECROSIS-FACTOR [TNF]-RELATED ACTIVATION-INDUCED CYTOKINE), A NEW TNF FAMILY MEMBER PREDOMINANTLY EXPRESSED IN T-CELLS, IS A DENDRITIC CELL-SPECIFIC SURVIVAL FACTOR

TRANCE (turner necrosis factor [TNF]-related activation-induced cytoki ne) is a new member of the TNF family that is induced upon T cell rece ptor engagement and activates c-Jun N-terminal kinase (JNK) after inte raction with its putative receptor (TRANCE-R). In addition, TRANCE exp ression is restricted to lymphoid organs and T cells. Here, we show th at high levels of TRANCE-R are detected on mature dendritic cells (DCs ) but not on freshly isolated B cells, T cells, or macrophages. Signal ing by TRANCE-R appears to be dependent on TNF receptor-associated fac tor 2 (TRAF2), since JNK induction is impaired in cells from transgeni c mice overexpressing a dominant negative TRAF2 protein. TRANCE inhibi ts apoptosis of mouse bone marrow-derived DCs and human monocyte-deriv ed DCs in vitro. The resulting increase in DC survival rr accompanied by a proportional increase in DC-mediated T cell proliferation in a mi xed leukocyte reaction. TRANCE upregulates Bcl-x(L) expression, sugges ting a potential mechanism for enhanced DC survival. TRANCE does not i nduce the proliferation of or increase the survival of T or B cells. T herefore, TRANCE is a new DC-restricted survival factor that mediates T cell-DC communication and may provide a tool to selectively enhance DC activity.