title: Decreased frequency of CD73+CD8+ T cells of HIV-infected patients correlates with immune activation and T cell exhaustion.
abstract: 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.
authors.affiliation: 1.Section Infectious Diseases, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. julianszw@gmail.com.
authors.forename: Ilona
authors.initials: I
authors.lastname: Tóth
authors.forename: Anh Q
authors.initials: AQ
authors.lastname: Le
authors.forename: Philip
authors.initials: P
authors.lastname: Hartjen
authors.forename: Adriana
authors.initials: A
authors.lastname: Thomssen
authors.forename: Verena
authors.initials: V
authors.lastname: Matzat
authors.forename: Clara
authors.initials: C
authors.lastname: Lehmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Scheurich
authors.forename: Claudia
authors.initials: C
authors.lastname: Beisel
authors.forename: Philipp
authors.initials: P
authors.lastname: Busch
authors.forename: Olaf
authors.initials: O
authors.lastname: Degen
authors.forename: Ansgar W
authors.initials: AW
authors.lastname: Lohse
authors.forename: Thomas
authors.initials: T
authors.lastname: Eiermann
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.forename: Dirk
authors.initials: D
authors.lastname: Meyer-Olson
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bockhorn
authors.forename: Joachim
authors.initials: J
authors.lastname: Hauber
authors.forename: Jan
authors.initials: J
authors.lastname: van Lunzen
authors.forename: Julian
authors.initials: J
authors.lastname: Schulze Zur Wiesch
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000328:Adult; D000818:Animals; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D002451:Cell Compartmentation / Q000276:immunology; D049109:Cell Proliferation; D018450:Disease Progression; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007376:Interleukin-2 / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D051379:Mice; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000821:virology; D055815:Young Adult
chemical_list: D007376:Interleukin-2; D015720:5'-Nucleotidase
keywords: 5′-ectonucleotidase; CD39; adenosine; elite controller; regulatory T cell