Phenotype, function, and gene expression profiles of programmed death-1hi cd8 t cells in healthy human adults

Jaikumar Duraiswamy, Chris C. Ibegbu, David Masopust, Joseph D. Miller, Koichi Araki, Gregory H. Doho, Pramila Tata, Satish Gupta, Michael J. Zilliox, Helder I. Nakaya, Bali Pulendran, W. Nicholas Haining, Gordon J. Freeman, Rafi Ahmed

Research output: Contribution to journalArticlepeer-review

143 Scopus citations

Abstract

T cell dysfunction is an important feature of many chronic viral infections. In particular, it was shown that programmed death-1 (PD-1) regulates T cell dysfunction during chronic lymphocytic choriomeningitis virus infection in mice, and PD-1hi cells exhibit an intense exhausted gene signature. These findings were extended to human chronic infections such as HIV, hepatitis C virus, and hepatitis B virus. However, it is not known if PD-1 hi cells of healthy humans have the traits of exhausted cells. In this study, we provide a comprehensive description of phenotype, function, and gene expression profiles of PD-1hi versus PD-1lo CD8 T cells in the peripheral blood of healthy human adults as follows: 1) the percentage of naive and memory CD8 T cells varied widely in the peripheral blood cells of healthy humans, and PD-1 was expressed by the memory CD8 T cells; 2) PD-1hi CD8 T cells in healthy humans did not significantly correlate with the PD-1hi exhausted gene signature of HIV-specific human CD8 T cells or chronic lymphocytic choriomeningitis virus-specific CD8 T cells from mice; 3) PD-1 expression did not directly affect the ability of CD8 T cells to secrete cytokines in healthy adults; 4) PD-1 was expressed by the effector memory compared with terminally differentiated effector CD8 T cells; and 5) finally, an interesting inverse relationship between CD45RA and PD-1 expression was observed. In conclusion, our study shows that most PD-1hi CD8 T cells in healthy adult humans are effector memory cells rather than exhausted cells.

Original languageEnglish (US)
Pages (from-to)4200-4212
Number of pages13
JournalJournal of Immunology
Volume186
Issue number7
DOIs
StatePublished - Apr 1 2011

Bibliographical note

Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.

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