Enhanced PD-1 expression by T cells in cerebrospinal fluid does not reflect functional exhaustion during chronic human immunodeficiency virus type 1 infection.

Sadagopal S, Lorey SL, Barnett L, Sutherland D, Basham R, Erdem H, Kalams SA, Haas DW
J Virol. 2010 84 (1): 131-40

PMID: 19828602 · PMCID: PMC2798447 · DOI:10.1128/JVI.01181-09

During chronic viral infections, T cells are exhausted due to constant antigen exposure and are associated with enhanced programmed death 1 (PD-1) expression. Deficiencies in the PD-1/programmed death-ligand 1 (PD-L1) pathway are associated with autoimmune diseases, including those of the central nervous system (CNS). To understand the role of PD-1 expression in regulating T-cell immunity in the CNS during chronic infection, we characterized PD-1 expression in cerebrospinal fluid (CSF) and blood of individuals with chronic human immunodeficiency virus type 1 (HIV-1) infection. PD-1 expression was higher on HIV-specific CD8(+) T cells than on total CD8(+) T cells in both CSF and blood. PD-1 expression on CSF T cells correlated positively with CSF HIV-1 RNA and inversely with blood CD4(+) T-cell counts, suggesting that HIV-1 infection drives higher PD-1 expression on CSF T cells. However, in every HIV-positive individual, PD-1 expression was higher on T cells in CSF than on those in blood, despite HIV-1 RNA levels being lower. Among healthy HIV-negative controls, PD-1 expression was higher in CSF than in blood. Furthermore, frequencies of the senescence marker CD57 were lower on CSF T cells than on blood T cells, consistent with our prior observation of enhanced ex vivo functional capacity of CSF T cells. The higher PD-1 expression level on CSF T cells therefore does not reflect cellular exhaustion but may be a mechanism to downregulate immune-mediated tissue damage in the CNS. As inhibition of the PD-1/PD-L1 pathway is pursued as a therapeutic option for viral infections, potential effects of such a blockade on development of autoimmune responses in the CNS should be considered.

MeSH Terms (17)

Antigens, CD Apoptosis Regulatory Proteins Blood Cells Case-Control Studies CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes CD57 Antigens Cellular Senescence Central Nervous System Cerebrospinal Fluid Chronic Disease Gene Expression Regulation HIV Infections Humans Programmed Cell Death 1 Receptor RNA, Viral T-Lymphocytes

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