Role of thrombospondin-1 in T cell response to ocular pigment epithelial cells

Yuri Futagami, Sunao Sugita, Jose Vega, Kazuhiro Ishida, Hiroshi Takase, Kazuichi Maruyama, Hiroyuki Aburatani, Manabu Mochizuki

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

Ocular pigment epithelium (PE) cells promote the generation of T regulators (PE-induced Treg cells). Moreover, T cells exposed to PE acquire the capacity to suppress the activation of bystander T cells via TGFβ. Membrane-bound TGFβ on iris PE cells interacts with TGFβ receptors on T eels, leading to the conversion of T cells to CD8+ Treg cells via a cell contact-dependent mechanism. Conversely, soluble forms of TGFβ produced by retinal PE cells can convert CD4+ T cells into Treg cells in a manner that is independent of cell contact In this study, we looked at the expression of immunoregulatory factors (TGFβ, thrombospondins, CD59, IL-1 receptor antagonist, etc.) in PE cells as identified via an oligonucleotide microarray. Several thrombospondin-binding molecules were detected, and thus we focused subsequent analyses on thrombospondins. Via the conversion off latent TGFβ to an active form that appears to be mediated by thrombospondin 1 (TSP-1), cultured iris PE and retinal PE cells induce a PE-induced Treg cell fate. After conversion, both ocular PE and PE-induced Treg cells express TSP-1. Regulatory T cell generation was amplified when the T cells also expressed TSP-1. In addition, PE-induced Treg cells significantly suppressed activation of bystander T cells via TSP-1. These results strongly suggest that the ability of ocular PE and PE-induced Treg cells to suppress bystander T cells depends on their capacity to produce TSP-1. Thus, intraocular TSP-1 produced by both ocular parenchymal cells and regulatory T cells is essential for immune regulation in the eye.

Original languageEnglish
Pages (from-to)6994-7005
Number of pages12
JournalJournal of Immunology
Volume178
Issue number11
DOIs
Publication statusPublished - 2007 Jun 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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