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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, Vol. 94, No. 4, 01.10.2013, p. 551-61.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Tóth, I, Le, AQ, Hartjen, P, Thomssen, A, Matzat, V, Lehmann, C, Scheurich, C, Beisel, C, Busch, CP, Degen, O, Lohse, AW, Eiermann, T, Fätkenheuer, G, Meyer-Olson, D, Bockhorn, M, Hauber, J, Lunzen, J & Schulze Zur Wiesch, J 2013, 'Decreased frequency of CD73+CD8+ T cells of HIV-infected patients correlates with immune activation and T cell exhaustion', J LEUKOCYTE BIOL, vol. 94, no. 4, pp. 551-61. https://doi.org/10.1189/jlb.0113018

APA

Tóth, I., Le, A. Q., Hartjen, P., Thomssen, A., Matzat, V., Lehmann, C., Scheurich, C., Beisel, C., Busch, C. P., Degen, O., Lohse, A. W., Eiermann, T., Fätkenheuer, G., Meyer-Olson, D., Bockhorn, M., Hauber, J., Lunzen, J., & Schulze Zur Wiesch, J. (2013). Decreased frequency of CD73+CD8+ T cells of HIV-infected patients correlates with immune activation and T cell exhaustion. J LEUKOCYTE BIOL, 94(4), 551-61. https://doi.org/10.1189/jlb.0113018

Vancouver

Tóth I, Le AQ, Hartjen P, Thomssen A, Matzat V, Lehmann C et al. Decreased frequency of CD73+CD8+ T cells of HIV-infected patients correlates with immune activation and T cell exhaustion. J LEUKOCYTE BIOL. 2013 Oct 1;94(4):551-61. https://doi.org/10.1189/jlb.0113018

Bibtex

@article{e4b889d5654a43a788252bd481c2cb75,
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.",
keywords = "5'-Nucleotidase, Adult, Animals, Antiretroviral Therapy, Highly Active, CD8-Positive T-Lymphocytes, Cell Compartmentation, Cell Proliferation, Disease Progression, HIV Infections, Humans, Immunologic Memory, Interleukin-2, Lymph Nodes, Lymphocyte Activation, Lymphocyte Count, Lymphocyte Subsets, Mice, Middle Aged, T-Lymphocytes, Regulatory, Young Adult",
author = "Ilona T{\'o}th and Le, {Anh Q} and Philip Hartjen and Adriana Thomssen and Verena Matzat and Clara Lehmann and Christoph Scheurich and Claudia Beisel and Busch, {Christoph Philipp} and Olaf Degen and Lohse, {Ansgar W} and Thomas Eiermann and Gerd F{\"a}tkenheuer and Dirk Meyer-Olson and Maximilian Bockhorn and Joachim Hauber and Jan Lunzen and {Schulze Zur Wiesch}, Julian",
year = "2013",
month = oct,
day = "1",
doi = "10.1189/jlb.0113018",
language = "English",
volume = "94",
pages = "551--61",
journal = "J LEUKOCYTE BIOL",
issn = "0741-5400",
publisher = "FASEB",
number = "4",

}

RIS

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 -