Resistance of cultured peripheral T cells towards activation‐induced cell death involves a lack of recruitment of FLICE (MACH/caspase 8) to the CD95 death‐inducing signaling complex

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Abstract
Phytohemagglutinin‐activated peripheral CD95+ T cells (day 1 T cells) are resistant to CD95‐mediated apoptosis. After prolonged interleukin‐2 treatment, these T cells become CD95‐mediated apoptosis‐sensitive (day 6T cells). To elucidate the molecular mechanism of apoptosis resistance, day 1 and day 6 T cells were tested for formation of the CD95 death‐inducing signaling complex (DISC). DISC‐associated active Fas‐associated DD protein (FADD)‐like interleukin‐1β‐converting enzyme‐like protease (FLICE) also referred to as MACH/caspase 8 was only found in apoptosis‐sensitive day 6 T cells. Further analysis of mRNA and protein expression levels of apoptosis‐signaling molecules FADD, receptor interacting protein, hematopoietic cell protein tyrosine phosphatase, Fas‐associated phosphatase‐1, FLICE, bcl‐2, bcl‐xL, and, bax‐α showed that only the expression level of bcl‐xL correlated with T cell resistance to CD95‐mediated apoptosis (day 1 T cells: bcl‐xhiL; day 6 T cells: bcl‐xloL). In T cells activated in vitro, up‐regulation of bcl‐xL has previously been correlated with general apoptosis resistance. However, the experiments presented suggest that resistance to CD95‐mediated apoptosis in T cells can also be regulated at the level of recruitment of FLICE to the DISC.