Human iris pigment epithelium suppresses activation of bystander T cells via TGFbeta-TGFbeta receptor interaction.
Iris pigment epithelial (IPE) cells from the anterior segment in the eye are able to suppress activation of bystander responder T cells in vitro. The cultured IPE cells fully suppress proliferation and cytokine production by responder T cells via direct cell-to-cell contact. We have now investigated whether primary cultured human iris pigment epithelial (h-IPE) cells that were established from fresh iris tissues can also inhibit the activation of T cells in vitro. We found that cultured h-IPE cells significantly inhibited T cell proliferation and the IFN-gamma production by the target T cells from both the allogeneic and autogeneic peripheral blood mononuclear cells (PBMCs). The h-IPE cells also inhibited the activation of CD4(+) T cells from patients with active uveitis. The suppression by h-IPE occurred in a completely contact-dependent manner. The h-IPE constitutively expressed transforming growth factor beta (TGFbeta) and the receptors, and the T cells exposed to h-IPE greatly expressed Smad transcripts. In addition, TGFbeta2-siRNA transfected h-IPE failed to inhibit activation of responder T cells. Similarly, h-IPE cells in the presence of anti-TGFbeta neutralizing antibodies or recombinant TGFbeta receptor blocking proteins failed to inhibit the T-cell activation. In conclusion, cultured human iris pigment epithelium fully inhibits T cell activation in vitro. Our data support the hypothesis that the ocular resident cells play a critical role in immunosuppression in the eye.
Horie
Shintaro
S
Department of Ophthalmology & Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Sugita
Sunao
S
Futagami
Yuri
Y
Kawaguchi
Tastushi
T
Kamoi
Koju
K
Shirato
Shiroaki
S
Mochizuki
Manabu
M
D024201:Bystander Effect / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007498:Iris / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D010857:Pigment Epithelium of Eye / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D051785:Smad Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta