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Tomomi Nishida, Andrew W. Taylor; Specific Aqueous Humor Factors Induce Activation of Regulatory T Cells. Invest. Ophthalmol. Vis. Sci. 1999;40(10):2268-2274.
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purpose. To examine the possibility that aqueous humor–induced regulatory T
cells could function in vivo, these T cells were examined for their
ability to suppress adoptive transfer of delayed-type hypersensitivity
(DTH). To begin to understand the mechanisms by which aqueous humor
induces activation of regulatory T cells, α-melanocyte stimulating
hormone (MSH) and transforming growth factor (TGF)-β2 were examined
for ability to induce regulatory T cells.
methods. Primed T cells were treated with aqueous humor and assayed for
regulatory activity by injecting them intravenously along with
DTH-mediating T cells into syngeneic mice. Antigen-pulsed
antigen-presenting cells (APCs) were injected into the pinna of the
mouse ear, and swelling was measured 24 hours later. Primed T cells
were also activated in vitro in the presence of α-MSH, TGF-β1, or
TGF-β2 and were assayed for proliferation and TGF-β production
along with suppressing DTH.
results. Aqueous humor–treated T cells suppressed inflammation mediated by DTH
T cells. Maximum regulatory T cell activity was induced when primed T
cells were activated in vitro in the presence of α-MSH followed 4
hours later with active TGF-β2. Such T cells proliferated, produced
TGF-β, and suppressed DTH, suggesting that α-MSH and TGF-β2
induce activation of regulatory T cells. No regulatory T cell activity
could be induced in the presence of TGF-β1.
conclusions. The ocular microenvironment constitutively produces immunoregulatory
factors that suppress the induction of inflammatory activity and
promotes regulatory T cell activity. Such regulatory T cells can
further contribute to maintaining the normal immunosuppressive ocular
microenvironment through their ability to suppress activation of other
inflammatory T cells.
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