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High production rates sustain in vivo levels of PD-1high simian immunodeficiency virus-specific CD8 T cells in the face of rapid clearance

Petrovas, C., Yamamoto, T., Price, David, Rao, S., Klatt, N., Brenchley, J., Douek, D., Gostick, Emma, Angermann, B., Grossman, Z., Macallan, D., Meier-Schellersheim, M. and Koup, R. 2013. High production rates sustain in vivo levels of PD-1high simian immunodeficiency virus-specific CD8 T cells in the face of rapid clearance. Journal of Virology 87 (17) , pp. 9836-9844. 10.1128/JVI.01001-13

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Abstract

Programmed Death 1 (PD-1) expression by human/simian immunodeficiency virus (HIV/SIV)-specific CD8 T cells has been associated with defective cytokine production and reduced in vitro proliferation capacity. However, the cellular mechanisms that sustain PD-1high virus-specific CD8 T cell responses during chronic infection are unknown. Here, we show that the PD-1high phenotype is associated with accelerated in vivo CD8 T cell turnover in SIV-infected rhesus macaques, especially within the SIVspecific CD8 T cell pool. Mathematical modeling of 5-bromo-2= deoxyuridine (BrdU) labeling dynamics demonstrated a significantly increased generation rate of PD-1high compared to PD-1low CD8 T cells in all memory compartments. Simultaneous analysis of Ki67 and BrdU kinetics revealed a complex in vivo turnover profile whereby only a small fraction of PD-1high cells, but virtually all PD-1low cells, returned to rest after activation. Similar kinetics operated in both chronic and acute SIV infection. Our data suggest that the persistence of PD-1high SIV-specific CD8 T cells in chronic infection is maintained in vivo by a mechanism involving high production coupled with a high disappearance rate.

Item Type: Article
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RZ Other systems of medicine
Uncontrolled Keywords: Acute Disease; Animals; CD8-Positive T-Lymphocytes; Cell Proliferation; Chronic Disease; Cytokines; G0 Phase; Immunologic Memory; Lymphocyte Activation; Macaca mulatta; Programmed Cell Death 1 Receptor; Simian Acquired Immunodeficiency Syndrome; Simian immunodeficiency virus; T-Lymphocyte Subsets
Publisher: American Society for Microbiology
ISSN: 0022-538X
Date of First Compliant Deposit: 21 June 2016
Last Modified: 04 Jun 2017 09:05
URI: http://orca.cf.ac.uk/id/eprint/90311

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