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21383243
Phenotype, function, and gene expression profiles of programmed death-1(hi) CD8 T cells in healthy human adults.

J Immunol, 2011/4/01;186(7):4200-12.

Duraiswamy J[1], Ibegbu CC, Masopust D, Miller JD, Araki K, Doho GH, Tata P, Gupta S, Zilliox MJ, Nakaya HI, Pulendran B, Haining WN, Freeman GJ, Ahmed R

Affiliations

PMID: 21383243DOI: 10.4049/jimmunol.1001783

Impact factor: 5.426

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-1(hi) 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-1(hi) versus PD-1(lo) 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-1(hi) CD8 T cells in healthy humans did not significantly correlate with the PD-1(hi) 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-1(hi) CD8 T cells in healthy adult humans are effector memory cells rather than exhausted cells.
MeSH terms
Adult; Animals; Antigens, CD; Apoptosis Regulatory Proteins; CD8-Positive T-Lymphocytes; Down-Regulation; Gene Expression Profiling; Humans; Immunologic Memory; Immunophenotyping; Lymphocyte Activation; Lymphocyte Count; Lymphocytic choriomeningitis virus; Mice; Oligonucleotide Array Sequence Analysis; Programmed Cell Death 1 Receptor; Resting Phase, Cell Cycle; T-Lymphocyte Subsets; Up-Regulation
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