PURPOSE. Despite ocular immune privilege, (auto)immune-mediated acute anter
ior uveitis (AAU) is relatively common. However, although relapses of AAU a
re usually self-limiting, possible regulatory mechanisms remain undefined i
n humans. Experimentally, Fas-Ligand (FasL)-mediated apoptosis of Fast infl
ammatory cells contributes to the immune privilege within the anterior cham
ber anti provides an explanation for the success of corneal allograft trans
plantation. Therefore, whether such mechanisms regulate the immune response
in AAU was investigated.
METHODS. Aqueous and peripheral blood samples from consecutive patients pre
senting with idiopathic AAU were obtained with consent. Leukocytic phenotyp
e was analyzed by flow cytometry, and apoptosis was determined by both flow
cytometry and TdT-dUTP terminal nick-end labeling analysis. Presence of so
luble Fas and Fast was determined by western blot :analysis and enzyme-link
ed immunosorbent assay and compared with control aqueous from patients unde
rgoing cataract surgery. The ability of the aqueous to induce apoptosis in
a. Fas(+) Jurkat cell line was also determined.
RESULTS. During AAU aqueous-infiltrating Fas(+) cells included DD3(+) T cel
ls and granulocytes, whereas FasL(+) cells comprised predominantly of non-C
D3(+) T cells. Higher levels of functional soluble Fast were found in aqueo
us of AAU patients than in normal aqueous, capable of inducing apoptosis in
68.9% +/- 7.6% of Fas(+) lymphoid cells. Compared with peripheral blood, t
he CD4(+) T cells infiltrate within aqueous showed significantly increased
CD69 and CD25(IL-2r) expression. Flow cytometric analysis of aqueous showed
that 9.32% +/- 1.2% of infiltrating non-granulocyte CD45(+) cells were apo
ptotic, confirmed as T cells on subsequent three-color flow cytometric anal
ysis.
CONCLUSIONS. Taken together with published experimental data, the present s
tudy provides evidence for FasL-mediated apoptotic cell death contributing
to the local immune regulation BE ocular inflammatory disease and provides
a mechanism to account for the self-limiting clinical course of AAU.