SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection.

Journal article

Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion. Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested. PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression. SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation. While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells. PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation. Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death. Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection.

Authors: Petrovas, C; Price, D; Mattapallil, J; Ambrozak, DR; Geldmacher, C

• Publication status: Published
• Journal: Blood
• Volume: 110
• Issue: 3
• Pages: 928-936
• Publication date: 2007-08-01
• DOI: 10.1182/blood-2007-01-069112
• EISSN: 1528-0020
• ISSN: 0006-4971
• Language: English
• Keywords: Antigens, CD; Cell Differentiation; Cells, Cultured; CD8-Positive T-Lymphocytes; Simian immunodeficiency virus; Macaca mulatta; Cell Proliferation; Cytokines; Epitopes; Antigens, Viral; Apoptosis Regulatory Proteins; Peptides; Animals; Gene Expression Regulation; Simian Acquired Immunodeficiency Syndrome; Cell Death