CD59 cross-linking induces secretion of APO2 ligand in overactivated humanT cells

Jurkat cells and the derived TCR/CD3-defective subline, J.RT3.T3.5 undergo activation-induced cell death (AICD) when stimulated with phytohemagglutini n (PHA). Since J.RT3.T3.5 cells do not express antigen receptor, we searche d for the molecules that could be ligated by PHA and induce AICD in this ce ll line. We show here that the glycosyiphosphatidylinositol-linked CD59 mol ecule is expressed at the surface of Jurkat and J.RT3.T3.5 cells, and when cross-linked by specific antibodies can induce cell death. The toxicity of supernatants from PHA-stimulated Jurkat or J.RT3.T3.5 cells was prevented b y a combination of the blocking anti-fas mAb SM1/23 and anti-APO2L/TRAIL mA b 5C2. However, toxicity of supernatants from anti-CD59 stimulated cells wa s specifically prevented by the anti-APO2L blocking antibody. Anti-CD59 cro ss-linking induced AICD also in normal human T cell blasts, which secreted toxic molecules into the supernatant. The toxicity of these supernatants on Jurkat cells was fully prevented by the anti-APO2L blocking antibody, show ing that CD59 crosslinking induces the preferential release of APO2L also i n normal T cells. The possible physiological and/or pathological consequenc es of this observation are discussed.