Abstract
Murine retinal pigment epithelial (RPE) cells suppress T-cell activation by releasing soluble inhibitory factors and promote the generation of regulatory T cells in vitro. These T cells exposed to RPE supernatants (RPE-induced Treg cells) can suppress the activation of bystander effector T cells via the production of transforming growth factor-beta (TGFbeta). In the present study, we showed that human RPE-induced Treg cells are also able to acquire regulatory function when human RPE cell lines were pretreated with recombinant TGF beta 2. These RPE-induced Treg cells produced TGF beta 1 and IL-10 but not IFN gamma, and they significantly suppressed the activation of target cell lines and intraocular T-cell clones established from patients with active uveitis. Moreover, CD4(+)CD25(+) RPE-induced Treg cells expressed CTLA-4 and Foxp3 molecules, and the CD25(+) Treg cells profoundly suppressed the T-cell activation. Thus, in vitro manipulated Treg cells acquire functions that participate in the establishment of immune tolerance in the eye.
(c) 2010 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Cell Line
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Cell Proliferation
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Culture Media, Conditioned / pharmacology
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Dinoprostone / metabolism
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Epithelial Cells / drug effects
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Epithelial Cells / immunology
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Epithelial Cells / metabolism
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Eye / cytology
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Eye / immunology*
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Forkhead Transcription Factors / metabolism
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Gene Expression / drug effects
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Gene Expression / genetics
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Humans
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Immune Tolerance / immunology*
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Interferon-gamma / metabolism
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Interleukin-10 / metabolism
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Interleukin-2 Receptor alpha Subunit / metabolism*
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Lymphocyte Activation / immunology
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RNA, Small Interfering / genetics
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Receptors, Transforming Growth Factor beta / genetics
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Retinal Pigment Epithelium / cytology
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Retinal Pigment Epithelium / immunology*
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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T-Lymphocytes, Regulatory / drug effects
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism
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Th1 Cells / immunology
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Th1 Cells / metabolism
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Thrombospondin 1 / metabolism
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Transforming Growth Factor beta / antagonists & inhibitors
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Transforming Growth Factor beta / immunology
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Transforming Growth Factor beta1 / genetics
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Transforming Growth Factor beta1 / metabolism
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Transforming Growth Factor beta2 / genetics
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Transforming Growth Factor beta2 / metabolism
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Transforming Growth Factor beta2 / pharmacology
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Uveitis / immunology
Substances
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Antibodies, Monoclonal
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Culture Media, Conditioned
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FOXP3 protein, human
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Forkhead Transcription Factors
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IL10 protein, human
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IL2RA protein, human
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Interleukin-2 Receptor alpha Subunit
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RNA, Small Interfering
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Receptors, Transforming Growth Factor beta
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Thrombospondin 1
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Transforming Growth Factor beta2
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Interleukin-10
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Interferon-gamma
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Dinoprostone