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T-Cell Activation Independently Associates With Immune Senescence in HIV-Infected Recipients of Long-term Antiretroviral Treatment. / Cobos Jiménez, Viviana; Wit, Ferdinand W. N. M.; Joerink, Maaike et al.

In: Journal of infectious diseases, Vol. 214, No. 2, 2016, p. 216-225.

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@article{a9b6b7d16c3543de95e82525d1446178,
title = "T-Cell Activation Independently Associates With Immune Senescence in HIV-Infected Recipients of Long-term Antiretroviral Treatment",
abstract = "Aging-associated noncommunicable comorbidities are more prevalent among human immunodeficiency virus type 1 (HIV)-infected individuals than among HIV-uninfected individuals. Residual HIV-related chronic immune activation and senescence may increase the risk of developing comorbidities. Immune phenotyping, thymic output, and telomere length were assessed in 94 HIV-infected individuals who were aged >45 years and receiving antiretroviral therapy (ART; cases) and 95 age-matched uninfected controls. Cases had lower CD4(+) T-cell counts, higher CD8(+) T-cell counts, and increased levels of immune activation (ie, increased soluble CD14 [sCD14] level and increased percentages of CD38(+)HLA-DR(+) cells among both CD4(+) and CD8(+) T cells), regulatory T cells, and percentage of programmed cell death 1 (PD-1)-expressing cells among CD4(+) T cells. Immune senescence levels (ie, percentages of CD27(-)CD28(-) cells or CD57(+) cells) were comparable between cases and controls. Peripheral blood mononuclear cells from cases had shorter telomeres but increased single-joint T-cell receptor excision circle content and CD31(+) naive CD4(+) T cells. Although cytomegalovirus (CMV) antibody titers were higher in cases, CMV-specific T-cell responses were comparable between cases and controls. T-cell senescence in cases was independently associated with T-cell activation but not with CMV-specific immune responses. Despite long-term receipt of ART, HIV-infected adults had higher levels of immune activation, regulatory T cells, and PD-1-expressing CD4(+) cells and shorter telomeres. The increased soluble CD14 levels and percentage of CD38(+)HLA-DR(+) cells among CD4(+) T cells correlated with shorter telomeres and increased regulatory T-cell levels. This suggests that HIV influences immune function irreversibly, with several pathways that are persistently abnormal during effective ART. Therapies aimed at improving immune health during ART are needed",
author = "{Cobos Jim{\'e}nez}, Viviana and Wit, {Ferdinand W. N. M.} and Maaike Joerink and Irma Maurer and Harskamp, {Agnes M.} and Judith Schouten and Maria Prins and {van Leeuwen}, {Ester M. M.} and Thijs Booiman and Deeks, {Steven G.} and Peter Reiss and Kootstra, {Neeltje A.} and {AUTHOR GROUP} and {van der Valk}, M. and Kooij, {K. W.} and {van Zoest}, {R. A.} and Elsenga, {B. C.} and M. Prins and M. Martens and B. Boeser-Nunnink and Geerlings, {S. E.} and Godfried, {M. H.} and A. Goorhuis and Hovius, {J. W. R.} and Nellen, {F. J. B.} and {van der Meer}, {J. T. M.} and {van der Poll}, T. and Prins, {J. M.} and Wiersinga, {W. J.} and Postema, {P. G.} and Bisschop, {P. H. L. T.} and Serlie, {M. J. M.} and E. Dekker and {de Rooij}, {S. E. J. A.} and L. Vogt and P. Portegies and Schmand, {B. A.} and Geurtsen, {G. J.} and {van Eck-Smit}, {B. L. F.} and {de Jong}, M. and Richel, {D. J.} and Verbraak, {F. D.} and N. Demirkaya and Ruh{\'e}, {H. G.} and Nieuwkerk, {P. T.} and {van Steenwijk}, {R. P.} and Majoie, {C. B. L. M.} and Caan, {M. W. A.} and {van Lunsen}, {H. W.} and {van den Born}, {B. J. H.} and Stroes, {E. S. G.}",
year = "2016",
doi = "10.1093/infdis/jiw146",
language = "English",
volume = "214",
pages = "216--225",
journal = "Journal of infectious diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "2",

}

RIS

TY - JOUR

T1 - T-Cell Activation Independently Associates With Immune Senescence in HIV-Infected Recipients of Long-term Antiretroviral Treatment

AU - Cobos Jiménez, Viviana

AU - Wit, Ferdinand W. N. M.

AU - Joerink, Maaike

AU - Maurer, Irma

AU - Harskamp, Agnes M.

AU - Schouten, Judith

AU - Prins, Maria

AU - van Leeuwen, Ester M. M.

AU - Booiman, Thijs

AU - Deeks, Steven G.

AU - Reiss, Peter

AU - Kootstra, Neeltje A.

AU - AUTHOR GROUP

AU - van der Valk, M.

AU - Kooij, K. W.

AU - van Zoest, R. A.

AU - Elsenga, B. C.

AU - Prins, M.

AU - Martens, M.

AU - Boeser-Nunnink, B.

AU - Geerlings, S. E.

AU - Godfried, M. H.

AU - Goorhuis, A.

AU - Hovius, J. W. R.

AU - Nellen, F. J. B.

AU - van der Meer, J. T. M.

AU - van der Poll, T.

AU - Prins, J. M.

AU - Wiersinga, W. J.

AU - Postema, P. G.

AU - Bisschop, P. H. L. T.

AU - Serlie, M. J. M.

AU - Dekker, E.

AU - de Rooij, S. E. J. A.

AU - Vogt, L.

AU - Portegies, P.

AU - Schmand, B. A.

AU - Geurtsen, G. J.

AU - van Eck-Smit, B. L. F.

AU - de Jong, M.

AU - Richel, D. J.

AU - Verbraak, F. D.

AU - Demirkaya, N.

AU - Ruhé, H. G.

AU - Nieuwkerk, P. T.

AU - van Steenwijk, R. P.

AU - Majoie, C. B. L. M.

AU - Caan, M. W. A.

AU - van Lunsen, H. W.

AU - van den Born, B. J. H.

AU - Stroes, E. S. G.

PY - 2016

Y1 - 2016

N2 - Aging-associated noncommunicable comorbidities are more prevalent among human immunodeficiency virus type 1 (HIV)-infected individuals than among HIV-uninfected individuals. Residual HIV-related chronic immune activation and senescence may increase the risk of developing comorbidities. Immune phenotyping, thymic output, and telomere length were assessed in 94 HIV-infected individuals who were aged >45 years and receiving antiretroviral therapy (ART; cases) and 95 age-matched uninfected controls. Cases had lower CD4(+) T-cell counts, higher CD8(+) T-cell counts, and increased levels of immune activation (ie, increased soluble CD14 [sCD14] level and increased percentages of CD38(+)HLA-DR(+) cells among both CD4(+) and CD8(+) T cells), regulatory T cells, and percentage of programmed cell death 1 (PD-1)-expressing cells among CD4(+) T cells. Immune senescence levels (ie, percentages of CD27(-)CD28(-) cells or CD57(+) cells) were comparable between cases and controls. Peripheral blood mononuclear cells from cases had shorter telomeres but increased single-joint T-cell receptor excision circle content and CD31(+) naive CD4(+) T cells. Although cytomegalovirus (CMV) antibody titers were higher in cases, CMV-specific T-cell responses were comparable between cases and controls. T-cell senescence in cases was independently associated with T-cell activation but not with CMV-specific immune responses. Despite long-term receipt of ART, HIV-infected adults had higher levels of immune activation, regulatory T cells, and PD-1-expressing CD4(+) cells and shorter telomeres. The increased soluble CD14 levels and percentage of CD38(+)HLA-DR(+) cells among CD4(+) T cells correlated with shorter telomeres and increased regulatory T-cell levels. This suggests that HIV influences immune function irreversibly, with several pathways that are persistently abnormal during effective ART. Therapies aimed at improving immune health during ART are needed

AB - Aging-associated noncommunicable comorbidities are more prevalent among human immunodeficiency virus type 1 (HIV)-infected individuals than among HIV-uninfected individuals. Residual HIV-related chronic immune activation and senescence may increase the risk of developing comorbidities. Immune phenotyping, thymic output, and telomere length were assessed in 94 HIV-infected individuals who were aged >45 years and receiving antiretroviral therapy (ART; cases) and 95 age-matched uninfected controls. Cases had lower CD4(+) T-cell counts, higher CD8(+) T-cell counts, and increased levels of immune activation (ie, increased soluble CD14 [sCD14] level and increased percentages of CD38(+)HLA-DR(+) cells among both CD4(+) and CD8(+) T cells), regulatory T cells, and percentage of programmed cell death 1 (PD-1)-expressing cells among CD4(+) T cells. Immune senescence levels (ie, percentages of CD27(-)CD28(-) cells or CD57(+) cells) were comparable between cases and controls. Peripheral blood mononuclear cells from cases had shorter telomeres but increased single-joint T-cell receptor excision circle content and CD31(+) naive CD4(+) T cells. Although cytomegalovirus (CMV) antibody titers were higher in cases, CMV-specific T-cell responses were comparable between cases and controls. T-cell senescence in cases was independently associated with T-cell activation but not with CMV-specific immune responses. Despite long-term receipt of ART, HIV-infected adults had higher levels of immune activation, regulatory T cells, and PD-1-expressing CD4(+) cells and shorter telomeres. The increased soluble CD14 levels and percentage of CD38(+)HLA-DR(+) cells among CD4(+) T cells correlated with shorter telomeres and increased regulatory T-cell levels. This suggests that HIV influences immune function irreversibly, with several pathways that are persistently abnormal during effective ART. Therapies aimed at improving immune health during ART are needed

U2 - 10.1093/infdis/jiw146

DO - 10.1093/infdis/jiw146

M3 - Article

C2 - 27073222

VL - 214

SP - 216

EP - 225

JO - Journal of infectious diseases

JF - Journal of infectious diseases

SN - 0022-1899

IS - 2

ER -

ID: 2898009