PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression.

Day, C; Kaufmann, D; Kiepiela, P; Brown, J; Moodley, E; Reddy, S; Mackey, E; Miller, J; Leslie, A; DePierres, C; Mncube, Z; Duraiswamy, J; Zhu, B; Eichbaum, Q; Altfeld, M; Wherry, E; Coovadia, H; Goulder, P; Klenerman, P; Ahmed, R; Freeman, G; Walker, B

Journal article

PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression.

Abstract:: Functional impairment of T cells is characteristic of many chronic mouse and human viral infections. The inhibitory receptor programmed death 1 (PD-1; also known as PDCD1), a negative regulator of activated T cells, is markedly upregulated on the surface of exhausted virus-specific CD8 T cells in mice. Blockade of this pathway using antibodies against the PD ligand 1 (PD-L1, also known as CD274) restores CD8 T-cell function and reduces viral load. To investigate the role of PD-1 in a chronic human viral infection, we examined PD-1 expression on human immunodeficiency virus (HIV)-specific CD8 T cells in 71 clade-C-infected people who were naive to anti-HIV treatments, using ten major histocompatibility complex (MHC) class I tetramers specific for frequently targeted epitopes. Here we report that PD-1 is significantly upregulated on these cells, and expression correlates with impaired HIV-specific CD8 T-cell function as well as predictors of disease progression: positively with plasma viral load and inversely with CD4 T-cell count. PD-1 expression on CD4 T cells likewise showed a positive correlation with viral load and an inverse correlation with CD4 T-cell count, and blockade of the pathway augmented HIV-specific CD4 and CD8 T-cell function. These data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function. Moreover, this pathway of reversible T-cell impairment provides a potential target for enhancing the function of exhausted T cells in chronic HIV infection.

Publication status:: Published

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APA Style

Day, C., Kaufmann, D., Kiepiela, P., Brown, J., Moodley, E., Reddy, S., Mackey, E., Miller, J., Leslie, A., DePierres, C., Mncube, Z., Duraiswamy, J., Zhu, B., Eichbaum, Q., Altfeld, M., Wherry, E., Coovadia, H., Goulder, P., Klenerman, P., … Walker, B. (2006). PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature, 443(7109), 350–354.

MLA Style

Day, C., et al. “PD-1 Expression on HIV-Specific T Cells Is Associated with T-Cell Exhaustion and Disease Progression.” Nature, vol. 443, no. 7109, 2006, pp. 350–54.

Chicago Style

Day, C, D Kaufmann, P Kiepiela, J Brown, E Moodley, S Reddy, E Mackey, et al. 2006. “PD-1 Expression on HIV-Specific T Cells Is Associated with T-Cell Exhaustion and Disease Progression.” Nature 443 (7109): 350–54.
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