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

University of Oxford, Oxford, England, United Kingdom
Journal of Experimental Medicine (Impact Factor: 12.52). 11/2006; 203(10):2281-92. DOI: 10.1084/jem.20061496
Source: PubMed


Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. PD-1 expression was found to be low on naive CD8(+) T cells and increased on memory CD8(+) T cells according to antigen specificity. Memory CD8(+) T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8(+) T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. PD-1 expression was independent of maturational markers on memory CD8(+) T cells and was not directly associated with an inability to produce cytokines. Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8(+) T cells. Manipulation of PD-1 led to changes in the ability of the cells to survive and expand, which, over several days, affected the number of cells expressing cytokines. Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8(+) T cell numbers, but possibly not all functions in vivo.

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Available from: Joseph P Casazza
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    • "The virus basically utilizes the host's cellular machinery for its own replication leading to extensive viral and host interactions during its life cycle (Kitchen et al., 2001; Lawn et al., 2001; Valenti, 2001; An et al., 2004; Resh, 2005; Broder, 2009; Gandhi et al., 2010). Some of the cellular factors aid replication while others are inhibitory (Balzarini, 1994; Mohri et al., 2001; Benito et al., 2004; Petrovas et al., 2006; Appay et al., 2007; Samikkannu et al., 2010). All these mechanisms lead to chronic immune activation, the key factor in HIV-1 immunopathogenesis. "
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