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Takeshi Kezuka, J. Wayne Streilein; In Vitro Generation of Regulatory CD8+ T Cells Similar to those Found in Mice with Anterior Chamber–Associated Immune Deviation. Invest. Ophthalmol. Vis. Sci. 2000;41(7):1803-1811.
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purpose. When injected intravenously into naïve mice, peritoneal exudate
cells (PECs) incubated with ovalbumin (OVA) in the presence of
transforming growth factor (TGF)-β2 induce immune deviation similar
to that evoked by injection of OVA into the anterior chamber of the
eye. Intraocular antigen injection elicits two distinct populations of
regulatory T cells that impair delayed hypersensitivity (DH) by two
different mechanisms: a CD4+ T cell that suppresses the
induction of DH (afferent) and a CD8+ T cell that inhibits
DH expression. In an effort to understand the origin and mechanism of
action of these regulatory cells, CD8+ T cells from
OVA-specific T cell receptor (Tcr) transgenic mice (OT-1) were
methods. CD8+ T cells were harvested from Tcr transgenic OT-I mice
whose Tcr recognize an OVA peptide in the context of the class I major
histocompatibility complex molecule Kb. These cells were
stimulated in vitro with OVA-pulsed PECs exposed (or not) to TGF-β2,
then analyzed for their capacity to proliferate, to secrete various
cytokines, to lyse OVA-expressing target cells, and to regulate
bystander T cells in vitro and in vivo.
results. When OVA-pulsed PECs were used in vitro as stimulators, responding OT-I
T cells proliferated and preferentially secreted interferon (IFN)-γ,
interleukin (IL)-2, and tumor necrosis factor (TNF)-α, rather than
IL-4 and IL-10. When the stimulator PECs were pretreated with TGF-β2
and then pulsed with OVA, responding OT-I T cells proliferated even
more swiftly, but they secreted significantly less IFN-γ, IL-2, and
TNF-α, and no IL-4 or IL-10. OT-I T cells, which constitutively
display cytotoxicity toward OVA-expressing target cells, lost this
activity when stimulated with OVA-pulsed, TGF-β2–pretreated PECs.
Moreover, OT-I T cells stimulated in this manner displayed the capacity
to inhibit proliferation of OVA-primed T cells exposed to OVA in vitro
and to suppress in vivo the expression of OVA-triggered DH.
conclusions. OVA-pulsed PECs, pretreated with TGF-β2, coerce naïve
OVA-specific CD8+ T cells to become efferent regulators of
DH similar to the regulatory T cells evoked by intraocular injection of
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