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Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells

Citation

Goldberg, MV and Maris, CH and Hipkiss, EL and Flies, AS and Zhen, L and Tuder, RM and Grosso, JF and Harris, TJ and Getnet, D and Whartenby, KA and Brockstedt, DG and Dubensky Jr, TW and Chen, L and Pardoll, DM and Drake, CG, Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells, Blood, 110, (1) pp. 186-192. ISSN 0006-4971 (2007) [Refereed Article]

Copyright Statement

Copyright 2007 American Society of Hematology

DOI: doi:10.1182/blood-2006-12-062422

Abstract

Expression of the PD-1 receptor on T cells has been shown to provide an important inhibitory signal that down-modulates peripheral effector responses in normal tissues and tumors. Furthermore, PD-1 up-regulation on chronically activated T cells can maintain them in a partially reversible inactive state. The function of PD-1 in the very early stages of T-cell response to antigen in vivo has not been fully explored. In this study, we evaluate the role of PD-1 and its 2 B7 family ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), in early fate decisions of CD8 T cells. We show that CD8 T cells specific for influenza hemagglutinin (HA) expressed as a self-antigen become functionally tolerized and express high levels of surface PD-1 by the time of their first cell division. Blockade of PD-1 or B7-H1, but not B7-DC, at the time of self-antigen encounter mitigates tolerance induction and results in CD8 T-cell differentiation into functional cytolytic T lymphocytes (CTLs). These findings demonstrate that, in addition to modulating effector functions in the periphery, B7-H1:PD-1 interactions regulate early T-cell–fate decisions.

Item Details

Item Type:Refereed Article
Keywords:PD-1, B7-H1, PD-L1
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Cellular Immunology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
Author:Flies, AS (Dr Andy Flies)
ID Code:102796
Year Published:2007
Web of Science® Times Cited:106
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-09-07
Last Modified:2016-11-17
Downloads:0

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