Activation drives PD‐1 expression during vaccine‐specific proliferation and following lentiviral infection in macaques

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Abstract
Recent data supports that increased expression of PD‐1, a negative regulator of immune function, is associated with T cell exhaustion during chronic viral infection. However, PD‐1 expression during acute infection and vaccination has not been studied in great detail in primates. Here, we examine PD‐1 expression on CD3+ T cells following DNA vaccination or lentiviral infection of macaques. Ex vivo peptide stimulation of PBMC from DNA‐vaccinated uninfected macaques revealed a temporal increase in PD‐1 expression in proliferating antigen‐specific CD8+ T cells. Following the initial increase, PD‐1 expression steadily declined as proliferation continued, with a concomitant increase in IFN‐γ secretion. Subsequent examination of PD‐1 expression on T cells from uninfected and lentivirus‐infected non‐vaccinated macaques revealed a significant increase in PD‐1 expression with lentiviral infection, consistent with previous reports. PD‐1 expression was highest on cells with activated memory and effector phenotypes. Despite their decreased telomere length, PD‐1hi T cell populations do not appear to have statistically significant uncapped telomeres, typically indicative of proliferative exhaustion, suggesting a different mechanistic regulation of proliferation by PD‐1. Our data indicate that PD‐1 expression is increased as a result of T cell activation during a primary immune response as well as during persistent immune activation in macaques.Supporting Information for this article is available at www.wiley‐vch.de/contents/jc_2040/2008/37857_s.pdf