| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114
Pigment epithelial (PE) cells cultured from the eye possess the novel property of suppressing TCR-dependent activation of T cells in vitro. Iris PE (IPE) cells accomplish this suppression by a direct cell contact mechanism in which B7-2 expressed by the PE cells interacts with CTLA-4 on responding T cells. Because CTLA-4 expression is constitutively expressed on a very small proportion of naive splenic T cells and since exposure of splenic T cells to IPE leads to global T cell suppression, we have inquired into the mechanism by which suppression is achieved. Using splenic T cells and IPE from donor mice with disrupted genes for CD80 (B7-1), CD86 (B7-2), CTLA-4, and/or CD28, we report that B7-2+ IPE in the presence of anti-CD3 supported selectively the activation of CTLA-4+ CD8+ T cells that express their own B7-2 and secrete enhanced amounts of active TGF
. By contrast, activation of CTLA-4-negative T cells, especially CD4+ cells, in these cultures was profoundly suppressed. Because global suppression of T cell activation in these cultures was obtained only when both IPE and T cells possessed B7-2 genes and expressed the costimulators as surface molecules, we propose that T cells activated in the presence of parenchymal cells from the eye (an immune privileged site) express B7-2 in a manner that equips them to suppress bystander T cells. Thus, B7-2 expression on T cells participates in their eventual ability to function as regulators in vitro.
This article has been cited by other articles:
|
|
 |
|
  S. Sugita, Y. Usui, S. Horie, Y. Futagami, H. Aburatani, T. Okazaki, T. Honjo, M. Takeuchi, and M. Mochizuki T-Cell Suppression by Programmed Cell Death 1 Ligand 1 on Retinal Pigment Epithelium during Inflammatory Conditions Invest. Ophthalmol. Vis. Sci., June 1, 2009; 50(6): 2862 - 2870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sugita, Y. Usui, S. Horie, Y. Futagami, Y. Yamada, J. Ma, T. Kezuka, H. Hamada, T. Usui, M. Mochizuki, et al. Human Corneal Endothelial Cells Expressing Programmed Death-Ligand 1 (PD-L1) Suppress PD-1+ T Helper 1 Cells by a Contact-Dependent Mechanism Invest. Ophthalmol. Vis. Sci., January 1, 2009; 50(1): 263 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sugita, S. Horie, O. Nakamura, Y. Futagami, H. Takase, H. Keino, H. Aburatani, N. Katunuma, K. Ishidoh, Y. Yamamoto, et al. Retinal Pigment Epithelium-Derived CTLA-2{alpha} Induces TGF{beta}-Producing T Regulatory Cells J. Immunol., December 1, 2008; 181(11): 7525 - 7536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Futagami, S. Sugita, J. Vega, K. Ishida, H. Takase, K. Maruyama, H. Aburatani, and M. Mochizuki Role of Thrombospondin-1 in T Cell Response to Ocular Pigment Epithelial Cells J. Immunol., June 1, 2007; 178(11): 6994 - 7005. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Stein-Streilein and A. W. Taylor An eye's view of T regulatory cells J. Leukoc. Biol., March 1, 2007; 81(3): 593 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sugita, H. Keino, Y. Futagami, H. Takase, M. Mochizuki, J. Stein-Streilein, and J. W. Streilein B7+ Iris Pigment Epithelial Cells Convert T Cells into CTLA-4+, B7-Expressing CD8+ Regulatory T Cells Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5376 - 5384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sugita, T. F. Ng, P. J. Lucas, R. E. Gress, and J. W. Streilein B7+ Iris Pigment Epithelium Induce CD8+ T Regulatory Cells; Both Suppress CTLA-4+ T Cells J. Immunol., January 1, 2006; 176(1): 118 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Ono THE BIRTH OF TRANSPLANTATION IMMUNOLOGY: THE BILLINGHAM--MEDAWAR EXPERIMENTS AT BIRMINGHAM UNIVERSITY AND UNIVERSITY COLLEGE LONDON J. Exp. Biol., November 1, 2004; 207(23): 4013 - 4014. [Full Text] [PDF]
|
|
|
|
|
|
B. T. Rouse and S. Suvas Regulatory Cells and Infectious Agents: Detentes Cordiale and Contraire J. Immunol., August 15, 2004; 173(4): 2211 - 2215. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
