Dendritic cells prevent CD95 mediated T lymphocyte death through costimulatory signals

Abstract

T cell apoptosis is a mechanism regulating T cell homeostasis. Prolonged stimulation renders T cells susceptible to activation induced cell death (AICD), a process mediated through CD95 (Apo-1/Fas). While under some circumstances AICD can be prevented, little is known about molecules involved. Here, we wanted to assess whether dendritic cells (DC) have the capacity to prevent CD95-dependent AICD. T cells activated with PHA/PMA or anti-CD3 monoclonal antibody (mAb) were cocultured with increasing amounts of DC. While spontaneous T cell apoptosis amounted to 25%, the presence of an agonistic anti-CD95 antibody increased cell death to 64%. Addition of scalar amounts of DC prevented T cell apoptosis in a dose dependent fashion, where coculture of 105 DC/ml with 106 T cells/ml reduced apoptosis almost to baseline level (33%). Further addition of an anti-CD58 antibody partially abolished this protective effect. This was even more pronounced if anti-CD80 and anti-CD86 antibodies were added. Our findings suggest that dendritic cells are able to recue T cells from AICD, with CD58 ligation playing a key role.