PD-1 is a regulator of virus-specific CD8⁺ T cell survival in HIV infection

JEM, 203, 2281–2292 (2006)

Speaker：蔡宜文                                         Place：Room 601

Commentator：陳舜華  老師                   Date：2006/11/15 14:00-15:00

Abstract：

Programmed death (PD)-1 is a negative regulatory receptor induced on activated T, B and myeloid cells. It delivers an inhibitory cosignal by engagement of PD-L1 or PD-L2. Previous findings showed that the functional capacity of HIV-specific CD8⁺ T cells was adversely affected by HIV infection (1). However, blocking PD-1 offered an alternative approach to restore exhausted virus-specific CD8⁺ T cells in a mouse model of chronic lymphocytic choriomeningitis virus infection (2).  This paper addressed the question whether PD-1 plays a role for the function and survival of the HIV-specific CD8⁺ T cells in HIV infection.  Firstly, the authors showed that myeloid dendritic cells (mDCs) and monocytes regulated CD8⁺ T cell function through the expression of PD-1-specific ligands. PD-1 expression was found to be high on memory CD8⁺ T cells according to antigen specificity especially on HIV-specific CD8⁺ T cells.  Secondly, the authors found that the expression of PD-1 on HIV-specific CD8⁺ T cells was associated with the inability to survival and indirectly impaired their proliferation and cytokine production.  Importantly, in CD8⁺ T cells the PD-1 was the major determinant of apoptosis sensitivity.  This paper provided evidence that PD-1 plays a critical role in regulating CD8⁺ T cell response in HIV infection.

Reference：

1.      HIV nonprogressors preferentially maintain highly functional HIV-specific CD8⁺ T-cells. Blood. 107:4781–4789. (2006)

2.      Restoring function in exhausted CD8 T cells during chronic viral infection. Nature.439:682–687. (2006)