Role of thrombospondin-1 in T cell response to ocular pigment epithelial cells.
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 TGFbeta. Membrane-bound TGFbeta on iris PE cells interacts with TGFbeta receptors on T cells, leading to the conversion of T cells to CD8(+) Treg cells via a cell contact-dependent mechanism. Conversely, soluble forms of TGFbeta 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 (TGFbeta, 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 of latent TGFbeta 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.
Futagami
Yuri
Y
Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan.
Sugita
Sunao
S
Vega
Jose
J
Ishida
Kazuhiro
K
Takase
Hiroshi
H
Maruyama
Kazuichi
K
Aburatani
Hiroyuki
H
Mochizuki
Manabu
M
D000595:Amino Acid Sequence; D000818:Animals; D024201:Bystander Effect / Q000276:immunology; D002478:Cells, Cultured; D007155:Immunologic Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019700:Thrombospondin 1 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D007155:Immunologic Factors; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta