Setting Dendritic Cell Life-Span

Science's STKE  01 Jun 2004:
Vol. 2004, Issue 235, pp. tw195-TW195
DOI: 10.1126/stke.2352004TW195

Dendritic cells are stimulated by various ligands derived from foreign cells, detecting infection, and by ligands expressed by T cells. Hou and Parijs reported that exposure of immature dendritic cells in culture to either Toll-like receptor (TLR) ligands--lipoteichoic acid (LTA), which binds TLR2; lipopolysaccharide (LPS), which binds TLR; or cytosine-phosphate-guanine (CpG), which binds TLR9--or to T cell costimulatory molecules CD40 ligand (CD40L) or TRANCE (tumor necrosis factor-related activation-induced cytokine) increased short-term cell survival. The abundance of the antiapoptotic protein Bcl-XL was increased in response to each of these ligands and was required for the increased short-term viability of the cells (1 to 3 days). CpG also produced an increase in the antiapoptotic protein Bcl-2 that persisted throughout the time period (1 to 4 days). At longer time periods (past 3 days), cells exposed to LPS or LTA exhibited decreased viability, an increase in the abundance of the proapoptotic protein Bim, and a decrease in Bcl-2. Exposure to CpG did not result in decreased Bcl-2, and exposure to CD40L did not alter the abundance of either Bcl-2 or Bim. Thus, the balance of Bim and Bcl-2 may contribute to differences in the ability of the ligands to prolong the life-span of dendritic cells. In vitro, cells deficient in Bcl-2 activated T cells; however, in vivo, Bcl-2-deficient dendritic cells did not produce T cell responses that were as robust as those observed with wild-type dendritic cells. In addition, the abundance of Bcl-2-deficient dendritic cells in the spleen and lymph nodes was lower than that observed for wild-type dendritic cells. Finally, mice with Bcl-2-deficient dendritic cells showed an increase in spleen and lymph node dendritic cells when exposed to CD40-specific antibodies, but a decrease in lymphoid-associated dendritic cells when exposed to LPS. Thus, different dendritic cell-activating ligands appear to activate different pathways that govern the life-span of these cells (see Moser).

W.-S. Hou, L. V. Parijs, A Bcl-2-dependent molecular timer regulates the lifespan and immunogenicity of dendritic cells. Nat. Immunol. 5, 583-589 (2004). [Online Journal]

M. Moser, Balancing life and death. Nat. Immunol. 5, 559-560 (2004). [Online Journal]