Ca. White et al., THE ROLES OF FAS, FAS LIGAND AND BCL-2 IN T-CELL APOPTOSIS IN THE CENTRAL-NERVOUS-SYSTEM IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, Journal of neuroimmunology, 82(1), 1998, pp. 47-55
The selective apoptotic elimination of autoreactive T cells in the cen
tral nervous system (CNS) contributes to the resolution of inflammatio
n and the spontaneous clinical recovery from experimental autoimmune e
ncephalomyelitis (EAE). To assess the molecular mechanisms involved in
this process, we used three-colour flow cytometry to examine the expr
ession of apoptosis-regulating proteins by inflammatory cells isolated
from the spinal cords of Lewis rats immunized with myelin basic prote
in (MBP) and complete Freund's adjuvant. Throughout the course of the
disease, which peaked 12-14 days after inoculation and was followed by
clinical recovery, we analyzed the DNA content of the spinal cord inf
lammatory cells to assess apoptosis and, simultaneously, we measured t
he expression of five proteins (Fas, Fas ligand (Fas-L), Bcl-2, Bcl-x
and Bar) which modulate the apoptotic process. Cells expressing the de
ath effector molecules Fas and Fas-L were particularly prone to underg
o apoptosis, and were over-represented in the apoptotic population. Of
the cells expressing the cell death inhibitor Bcl-2, a low proportion
were undergoing apoptosis compared to the proportion of the total inf
lammatory cell population undergoing apoptosis, indicating that expres
sion of Bcl-2 protects against T cell apoptosis in this disease. There
was no evidence, however, that the apoptotic regulators Bcl-x and Bar
influenced the susceptibility to apoptosis. We also found that V beta
8.2(+) T cells, which constitute the predominant encephalitogenic MBP
-reactive T cell population in the Lewis rat, have a high frequency of
Fas and Fas-L expression compared to other inflammatory cells. This w
ould account for the previously demonstrated susceptibility of V beta
8.2(+) T cells to apoptosis in the CNS in EAE. These findings support
the hypothesis that autoreactive T cells are eliminated from the CNS d
uring spontaneous recovery from EAE by activation-induced apoptosis in
volving the Fas pathway. (C) 1998 Elsevier Science B.V.