Decreased frequency of CD73+CD8+ T cells of HIV-infected patients correlates with immune activation and T cell exhaustion
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Decreased frequency of CD73+CD8+ T cells of HIV-infected patients correlates with immune activation and T cell exhaustion. / Tóth, Ilona; Le, Anh Q; Hartjen, Philip; Thomssen, Adriana; Matzat, Verena; Lehmann, Clara; Scheurich, Christoph; Beisel, Claudia; Busch, Christoph Philipp; Degen, Olaf; Lohse, Ansgar W; Eiermann, Thomas; Fätkenheuer, Gerd; Meyer-Olson, Dirk; Bockhorn, Maximilian; Hauber, Joachim; Lunzen, Jan; Schulze Zur Wiesch, Julian.
in: J LEUKOCYTE BIOL, Jahrgang 94, Nr. 4, 01.10.2013, S. 551-61.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Decreased frequency of CD73+CD8+ T cells of HIV-infected patients correlates with immune activation and T cell exhaustion
AU - Tóth, Ilona
AU - Le, Anh Q
AU - Hartjen, Philip
AU - Thomssen, Adriana
AU - Matzat, Verena
AU - Lehmann, Clara
AU - Scheurich, Christoph
AU - Beisel, Claudia
AU - Busch, Christoph Philipp
AU - Degen, Olaf
AU - Lohse, Ansgar W
AU - Eiermann, Thomas
AU - Fätkenheuer, Gerd
AU - Meyer-Olson, Dirk
AU - Bockhorn, Maximilian
AU - Hauber, Joachim
AU - Lunzen, Jan
AU - Schulze Zur Wiesch, Julian
PY - 2013/10/1
Y1 - 2013/10/1
N2 - 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.
AB - 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.
KW - 5'-Nucleotidase
KW - Adult
KW - Animals
KW - Antiretroviral Therapy, Highly Active
KW - CD8-Positive T-Lymphocytes
KW - Cell Compartmentation
KW - Cell Proliferation
KW - Disease Progression
KW - HIV Infections
KW - Humans
KW - Immunologic Memory
KW - Interleukin-2
KW - Lymph Nodes
KW - Lymphocyte Activation
KW - Lymphocyte Count
KW - Lymphocyte Subsets
KW - Mice
KW - Middle Aged
KW - T-Lymphocytes, Regulatory
KW - Young Adult
U2 - 10.1189/jlb.0113018
DO - 10.1189/jlb.0113018
M3 - SCORING: Journal article
C2 - 23709688
VL - 94
SP - 551
EP - 561
JO - J LEUKOCYTE BIOL
JF - J LEUKOCYTE BIOL
SN - 0741-5400
IS - 4
ER -