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Munenori Yoshida, Takeshi Kezuka, J. Wayne Streilein; Participation of Pigment Epithelium of Iris and Ciliary Body in Ocular Immune Privilege. 2. Generation of TGF-β–Producing Regulatory T Cells. Invest. Ophthalmol. Vis. Sci. 2000;41(12):3862-3870. doi: https://doi.org/.
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purpose. To determine whether T cells exposed to cultured iris and ciliary body
pigment epithelial (I/CB PE) cells acquire the capacity to modify the
activation, differentiation, and effector functions of bystander T
cells, and if so, to identify the mechanism.
methods. T cells from naive BALB/c mice were cultured with I/CB PE cells,
x-irradiated, and used as regulators (a) of T-cell activation in vitro
and (b) of delayed hypersensitivity expression in vivo. Neutralizing
anti–TGF-β and –IL-10 antibodies were used to abolish regulatory
function. T-cell activation was assessed for proliferation by[ 3H]thymidine incorporation and for IL-2, IFN-γ, IL-4,
and IL-10 production by semi-quantitative RT-PCR for mRNA and by
supernatant analysis by ELISA. I/CB PE–exposed T cells were evaluated
for mRNA content of IFN-γ, IL-4, TNF-α, TGF-β1, TGF-β2, and
IL-10, and their supernatants were analyzed for content of TGF-β.
results. T cells exposed to I/CB PE cells inhibited anti-CD3–driven activation
of bystander naive T cells in vitro and suppressed the expression of
delayed hypersensitivity in vivo. Bystander T cells cocultured with
I/CB PE–exposed T cells failed to proliferate and secreted high levels
of IL-4 and IL-10 but low amounts of IL-2 and IFN-γ. Regulation of
bystander T-cell activation was mediated via enhanced secretion of
TGF-β by I/CB PE–exposed T cells.
conclusions. T cells exposed to cultured I/CB PE cells were induced to secrete
active and latent TGF-β, which conferred on the T cells the capacity
to inhibit the differentiation as well as the effector function of
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