Decreased frequency of CD73+CD8+ T cells of HIV-infected patients correlates with immune activation and T cell exhaustion

J Leukoc Biol. 2013 Oct;94(4):551-61. doi: 10.1189/jlb.0113018. Epub 2013 May 24.


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.

Keywords: 5′-ectonucleotidase; CD39; adenosine; elite controller; regulatory T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5'-Nucleotidase / metabolism*
  • Adult
  • Animals
  • Antiretroviral Therapy, Highly Active
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology*
  • CD8-Positive T-Lymphocytes / virology
  • Cell Compartmentation / immunology
  • Cell Proliferation
  • Disease Progression
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology*
  • Humans
  • Immunologic Memory / immunology
  • Interleukin-2 / metabolism
  • Lymph Nodes / pathology
  • Lymphocyte Activation / immunology*
  • Lymphocyte Count
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / virology
  • Mice
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / virology
  • Young Adult


  • Interleukin-2
  • 5'-Nucleotidase