Decreased frequency of CD73+CD8+ T cells of HIV-infected patients correlates with immune activation and T cell exhaustion
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- Ilona Tóth
- Department of Medicine, Section Infectious Diseases, University Medical Center Hamburg-Eppendorf , Germany
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- Anh Q Le
- Simon Fraser University , Vancouver, Canada
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- Philip Hartjen
- Department of Medicine, Section Infectious Diseases, University Medical Center Hamburg-Eppendorf , Germany
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- Adriana Thomssen
- Department of Medicine, Section Infectious Diseases, University Medical Center Hamburg-Eppendorf , Germany
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- Verena Matzat
- Department of Medicine, Section Infectious Diseases, University Medical Center Hamburg-Eppendorf , Germany
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- Clara Lehmann
- Department of Medicine, University Medical School , Cologne, Germany
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- Christoph Scheurich
- Department of Medicine, Section Infectious Diseases, University Medical Center Hamburg-Eppendorf , Germany
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- Claudia Beisel
- Department of Medicine, Section Infectious Diseases, University Medical Center Hamburg-Eppendorf , Germany
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- Philipp Busch
- Abdominal Surgery, University Medical Center Hamburg-Eppendorf , Germany
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- Olaf Degen
- Department of Medicine, Section Infectious Diseases, University Medical Center Hamburg-Eppendorf , Germany
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- Ansgar W Lohse
- Department of Medicine, Section Infectious Diseases, University Medical Center Hamburg-Eppendorf , Germany
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- Thomas Eiermann
- Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf , Germany
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- Gerd Fätkenheuer
- Department of Medicine, University Medical School , Cologne, Germany
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- Dirk Meyer-Olson
- Center for Immunology and Rheumatology Hannover Medical School , Hannover, Germany
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- Maximilian Bockhorn
- Abdominal Surgery, University Medical Center Hamburg-Eppendorf , Germany
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- Joachim Hauber
- Heinrich Pette Institute-Leibniz Institute for Experimental Virology , Hamburg, Germany
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- Jan van Lunzen
- Department of Medicine, Section Infectious Diseases, University Medical Center Hamburg-Eppendorf , Germany
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- Julian Schulze zur Wiesch
- Department of Medicine, Section Infectious Diseases, University Medical Center Hamburg-Eppendorf , Germany
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<jats:title>ABSTRACT</jats:title><jats:p>Recent studies indicate that murine Tregs highly express the ENTDP1, as well as the 5′-NT and thereby, suppress Teff function by extracellular adenosine production. Furthermore, CD73 seems to play a role as costimulatory molecule for T cell differentiation. In this study, we analyzed the expression of CD73 on peripheral and lymph nodal Teffs and Tregs in a cohort of 95 HIV patients at different stages of disease, including LTNP and ECs. In contrast to murine Tregs, CD73 was only expressed on a small minority (∼10%) of peripheral Tregs. In contrast, we see high expression of CD73 on peripheral CD8+ T cells. In HIV infection, CD73 is markedly reduced on all Teffs and Tregs, regardless of the memory subtype. On CD8+ T cells, a positive correlation between CD73 expression and CD4 counts (P=0.0003) was detected. CD73 expression on CD8+ T cells negatively correlated with HLA-DR (<0.0001) and PD1 (P=0.0457) expression. The lower CD73 expression on CD8+ T cells was partially reversible after initiation of ART (P=0.0016). Functionally, we observed that CD8+CD73+ T cells produce more IL-2 upon HIV-specific and unspecific stimulation than their CD73− counterparts and show a higher proliferative capacity. These data indicate that down-regulation of CD73 on CD8+ T cells correlates with immune activation and leads to functional deficits in HIV infection.</jats:p>
収録刊行物
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- Journal of Leukocyte Biology
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Journal of Leukocyte Biology 94 (4), 551-561, 2013-10-01
Oxford University Press (OUP)
