PD-1 Inhibits Antiviral Immunity at the Effector Phase in the Liver

J. Exp. Med. 2003,198(1), 39–50

Speaker : 盧 淑 君                       Commentator: 黎 煥 耀 教授

Time : 13:00-14:00, Nov. 26, 2003 (W3)

Place : Room 601

Abstract:

Both TCR signal and costimulatory signal are required to activate the naïve T cells. Effector T cells can be activated by either TCR signal or costimulatory signal alone (1). Programmed death-1（PD-1）, a negative regulator of the immune system, is a cell surface membrane protein of the immunoglobulin superfamily. PD-1 is predominantly expressed on activated T cells and may be involved in peripheral tolerance as well as central tolerance. PD-L1（B7-H1）and PD-L2（B7-DC）were ligands identified as immuno- inhibitory receptor for PD-1 (2). The PD-L1 is expressed on vascular endothelium of nonlymphoid tissues and their expression are broadly induced on APCs such as DCs, macrophages, and B cells. Liver nonparenchymal cells （LNPCs） including Kupffer cells and liver sinusoidal endothelial cells（LSECs） constitutively expressed a series of cell-surface molecules associated with antigen presentation, such as MHC class I and II, ICAM-1, B7–1, B7–2 (3) and PD-L1. LNPCs can inhibit proliferation and cell division of activated T cells in the liver and was suggested through the PD-1/PD-L1 system. The absence of PD-1 signal induces proliferation of effector T cells in the adenovirus-infected liver and resulted in rapid clearance of the virus. It is concluded that PD-1/PD-L1 system may play important roles in negative regulation of immune responses at the effector phase in liver. The temporary blockade of the PD-1 pathway may open new therapeutic approach for chronic viral infections.

References :

1.     Mullbacher A., Flynn K. Aspects of cytotoxic T cell memory. Immunol. Rev. 1996; 150:113–127.

2.     Nishimura H, Honjo T. PD-1: an inhibitory immunoreceptor involved in peripheral tolerance. Trends Immunol. 2001;22:265–268.

3.     Knolle PA, Limmer A. Neighborhood politics: the immunoregulatory function of organ-resident liver endothelial cells. Trends Immunol. 2001:22:432–437.