CD40-LIGATION-MEDIATED PROTECTION FROM APOPTOSIS OF A FAS-SENSITIVE HODGKINS-DISEASE-DERIVED CELL-LINE

Modulation of Fas expression and function by CD40 ligation was investi gated in the Fas-sensitive human Hodgkin's disease cell line HDLM2. Th e recombinant human trimeric soluble CD40L (sCD40L) protected this cel l line from apoptosis induced by an agonistic Fas antibody at all conc entrations tested. sCD40L also protected HDLM2 when added up to 2 h af ter Fas ligation. Apoptosis induced by a cell-permeable synthetic cera mide could not be prevented by sCD40L. Thus, CD40 ligation is likely t o intervene in the early phases of the Fas signal transduction pathway . When CD40 ligation preceded Fas ligation, it rendered the cells refr actory to Fas-induced apoptosis. sCD40L-mediated protection could not be attributed to reduction in surface Fas expression, increase in Bcl- 2 levels or to increase in the levels of soluble Fas isoforms.