Neuronal FasL induces cell death of encephalitogenic T lymphocytes

Apoptosis of inflammatory cells plays a crucial role in the recovery from a utoimmune CNS disease. However, the underlying mechanisms of apoptosis indu ction are as yet ill-defined. Here we report on the neuronal expression of Fast and its potential function in inducing T-cell apoptosis, Using a combi nation of facial nerve axotomy and passive transfer encephalomyelitis, the fate of CD4(+) encephalitogenic T cells engineered to express the gene for green fluorescent protein was followed. Fast gene transcripts and Fast prot ein were detected in neurons by in situ-hybridization and immunohistochemis try. T cells infiltrating preferentially the injured brain parenchyma were found in the immediate vicinity of Fast expressing neurons and even inside their perikarya, In contrast to neurons, T cells rapidly underwent apoptosi s, In co-cultures of hippocampal nerve cells and CD4(+) T lymphocytes, we c onfirmed expression of Fast in neurons and concomitant induction of T-cell death. Antibodies blocking neuronal Fast were shown to have a protective ef fect on T-cell survival. Thus, Fast expression by neurons in neuroinflammat ory diseases may constitute a pivotal mechanism underlying apoptosis of enc ephalitogenic T cells.