Human retinal pigment epithelium-induced CD4+CD25+ regulatory T cells suppress activation of intraocular effector T cells

Clin Immunol. 2010 Jul;136(1):83-95. doi: 10.1016/j.clim.2010.03.001. Epub 2010 Mar 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Line
  • Cell Proliferation
  • Culture Media, Conditioned / pharmacology
  • Dinoprostone / metabolism
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Eye / cytology
  • Eye / immunology*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Humans
  • Immune Tolerance / immunology*
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-2 Receptor alpha Subunit / metabolism*
  • Lymphocyte Activation / immunology
  • RNA, Small Interfering / genetics
  • Receptors, Transforming Growth Factor beta / genetics
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Thrombospondin 1 / metabolism
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Transforming Growth Factor beta2 / genetics
  • Transforming Growth Factor beta2 / metabolism
  • Transforming Growth Factor beta2 / pharmacology
  • Uveitis / immunology

Substances

  • Antibodies, Monoclonal
  • Culture Media, Conditioned
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL10 protein, human
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • RNA, Small Interfering
  • Receptors, Transforming Growth Factor beta
  • Thrombospondin 1
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta2
  • Interleukin-10
  • Interferon-gamma
  • Dinoprostone