SPONTANEOUS APOPTOSIS OF DENDRITIC CELLS IS EFFICIENTLY INHIBITED BY TRAP (CD40-LIGAND) AND TNF-ALPHA, BUT STRONGLY ENHANCED BY INTERLEUKIN-10

In the lymphoid tissues, adaptive immune responses are initiated by th e interaction of interdigitating dendritic cells (IDC) with naive T ce lls. To understand this interplay better, we used mature Langerhans ce lls (mLC), migrating from human epidermis, as the correlate of IDC ex vivo to evaluate the different effects of tumor necrosis factor (TNF)- alpha, TNF-related activation protein (TRAP; CD40-ligand) and interleu kin-10 (IL-10) on induction or prevention of apoptotic cell death in t hese cells. Spontaneous decrease of mLC viability in culture was due t o apoptosis, as determined by the appearance of typical morphological changes such as dilatation of the endoplasmic reticulum (ER), chromati n condensation and membrane blebbing. IL-10 strongly reduced mLC viabi lity, whereas TRAP and TNF-alpha facilitated the survival of mLC. Spon taneous DNA fragmentation was detectable after 24 h in culture. IL-10 led to an earlier onset of DNA fragmentation, whereas TRAP and TNF-alp ha delayed internucleosomal DNA cleavage. We found that IL-10-treated mLC were readily ingested and removed by macrophages. TNF-alpha and TR AP, in contrast, reduced engulfment of mLC by macrophages. Interesting ly, IL-10, even at low concentrations, reverted the effects of TNF-alp ha and TRAP in inhibiting mLC apoptosis. Furthermore, IL-10 led to the down-regulation of various surface antigens, especially of CD86 and C D54, whereas TNF-alpha and TRAP enhanced the expression of MHC class I and II antigens and of the accessory molecules CD40, CD54, CD80 and C D86. Taken together, these results show that mLC spontaneously undergo apoptosis in culture and that the progression of mLC to apoptosis is inhibited by TRAP and TNF-alpha, but accelerated by IL-10.