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S. Horie, S. Sugita, Y. Futagami, T. Kawaguchi, S. Shirato, M. Mochizuki; Human Iris Pigment Epithelium Suppresses Activation of Bystander T Cells via TGFβ- TGFβ Receptor Interaction. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2519. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To determine whether human iris pigment epithelial (h-IPE) cells can inhibit activation of T cell in vitro.
Primary cultured h-IPE cells were established from fresh iris tissues. Target activated T cells were established from autogeneic or allogeneic T cells from peripheral blood mononuclear cells (PBMCs). As another targets, T cell clones of patients with uveitis were established from ocular fluid by the limiting dilution. T-cell activation was assessed for proliferation by [3H]-thymidine incorporation or IFN-γ production by the target T cells. Expression of TGFβ, the receptors, and Smad genes for TGFβ signal pathway on h-IPE cells & T cells exposed to h-IPE was evaluated with RT-PCR, immunohistochemistry. TGFβ gene down-regulation with siRNA systems was used to abolish IPE-inhibitory function.
Primary cultured h-IPE significantly inhibited T cell proliferation and IFN-γ production by target T cells from both allogeneic and autogeneic PBMCs. The h-IPE also inhibited the activation of CD4+ T cells from patients with uveitis. The suppression by h-IPE was completely contact-dependent manner. The h-IPE cells constitutively expressed TGFβ and the receptors, and T cells exposed to h-IPE greatly expressed Smad transcripts. In addition, TGFβ2-siRNA or pretreated h-IPE cells failed to inhibit the T-cell activation.
Cultured human iris pigment epithelium fully inhibits T cell activation in vitro. The ocular resident cells play a critical role in immunosuppression in the eye.
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