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Terminal Differentiation of CD56(dim)CD16(+) Natural Killer Cells Is Associated with Increase in Natural Killer Cell Frequencies After Antiretroviral Treatment in HIV-1 Infection.

Abstract

HIV-1 infection results in immunological abnormalities of natural killer (NK) cells such as disturbed distribution of NK cell subsets and downmodulation of activating and upregulation of inhibitory receptors thereby diminishing NK cell killing capacity and cytokine secretion. Antiretroviral treatment (ART) is known to restore phenotype and functions of NK cells. However, the effects of ART on NK cell terminal differentiation, activation, and disturbed distribution have not been studied yet longitudinally. Here, we analyzed the effects of ART on these parameters of peripheral blood NK cells in a longitudinal as well as in a cross-sectional study. We observed that expanded CD56(-)CD16(+) NK cell frequency is inversely correlated with the frequency of CD56(dim)CD16(+) NK cells in treatment-naive HIV-1 patients. Loss of CD56(dim)CD16(+) and expansion of CD56(-)CD16(+) NK cells again restore to the levels of healthy controls after ART. Enhanced immune activation of different NK cell subsets is partially restored after ART. Terminal differentiation of CD56(dim)CD16(+) NK cells is enhanced after ART as measured by CD57 expression. Frequencies of CD57(+)CD56(dim)CD16(+) NK cells are directly correlated with the frequencies of total NK cells suggesting that an increase in the frequencies of CD57(+)CD56(dim)CD16(+) NK cells is reflected by increased frequencies of total NK cells after ART. Taken together these data demonstrate that ART has an effect on the immune restoration of NK cells and is enhanced in the terminal differentiation of CD56(dim)CD16(+) NK cells, which is associated with increased frequencies of total NK cells after ART.

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  • Authors+Show Affiliations

    ,

    1 Klinik für Immunologie und Rheumatologie , Medizinische Hochschule, Hannover, Germany . 2 Hannover Biomedical Research School (HBRS) , Medizinische Hochschule, Hannover, Germany .

    ,

    1 Klinik für Immunologie und Rheumatologie , Medizinische Hochschule, Hannover, Germany .

    ,

    1 Klinik für Immunologie und Rheumatologie , Medizinische Hochschule, Hannover, Germany . 2 Hannover Biomedical Research School (HBRS) , Medizinische Hochschule, Hannover, Germany .

    ,

    1 Klinik für Immunologie und Rheumatologie , Medizinische Hochschule, Hannover, Germany .

    1 Klinik für Immunologie und Rheumatologie , Medizinische Hochschule, Hannover, Germany . 2 Hannover Biomedical Research School (HBRS) , Medizinische Hochschule, Hannover, Germany .

    Source

    AIDS research and human retroviruses 31:12 2015 Dec pg 1206-12

    MeSH

    Anti-Retroviral Agents
    CD56 Antigen
    CD57 Antigens
    Cell Differentiation
    Cross-Sectional Studies
    GPI-Linked Proteins
    HIV Infections
    HIV-1
    Humans
    Killer Cells, Natural
    Longitudinal Studies
    Lymphocyte Subsets
    Receptors, IgG

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    26352913

    Citation

    Ahmad, Fareed, et al. "Terminal Differentiation of CD56(dim)CD16(+) Natural Killer Cells Is Associated With Increase in Natural Killer Cell Frequencies After Antiretroviral Treatment in HIV-1 Infection." AIDS Research and Human Retroviruses, vol. 31, no. 12, 2015, pp. 1206-12.
    Ahmad F, Tufa DM, Mishra N, et al. Terminal Differentiation of CD56(dim)CD16(+) Natural Killer Cells Is Associated with Increase in Natural Killer Cell Frequencies After Antiretroviral Treatment in HIV-1 Infection. AIDS Res Hum Retroviruses. 2015;31(12):1206-12.
    Ahmad, F., Tufa, D. M., Mishra, N., Jacobs, R., & Schmidt, R. E. (2015). Terminal Differentiation of CD56(dim)CD16(+) Natural Killer Cells Is Associated with Increase in Natural Killer Cell Frequencies After Antiretroviral Treatment in HIV-1 Infection. AIDS Research and Human Retroviruses, 31(12), pp. 1206-12. doi:10.1089/aid.2015.0115.
    Ahmad F, et al. Terminal Differentiation of CD56(dim)CD16(+) Natural Killer Cells Is Associated With Increase in Natural Killer Cell Frequencies After Antiretroviral Treatment in HIV-1 Infection. AIDS Res Hum Retroviruses. 2015;31(12):1206-12. PubMed PMID: 26352913.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Terminal Differentiation of CD56(dim)CD16(+) Natural Killer Cells Is Associated with Increase in Natural Killer Cell Frequencies After Antiretroviral Treatment in HIV-1 Infection. AU - Ahmad,Fareed, AU - Tufa,Dejene Milkessa, AU - Mishra,Neha, AU - Jacobs,Roland, AU - Schmidt,Reinhold E, Y1 - 2015/09/09/ PY - 2015/9/10/entrez PY - 2015/9/10/pubmed PY - 2016/8/30/medline SP - 1206 EP - 12 JF - AIDS research and human retroviruses JO - AIDS Res. Hum. Retroviruses VL - 31 IS - 12 N2 - HIV-1 infection results in immunological abnormalities of natural killer (NK) cells such as disturbed distribution of NK cell subsets and downmodulation of activating and upregulation of inhibitory receptors thereby diminishing NK cell killing capacity and cytokine secretion. Antiretroviral treatment (ART) is known to restore phenotype and functions of NK cells. However, the effects of ART on NK cell terminal differentiation, activation, and disturbed distribution have not been studied yet longitudinally. Here, we analyzed the effects of ART on these parameters of peripheral blood NK cells in a longitudinal as well as in a cross-sectional study. We observed that expanded CD56(-)CD16(+) NK cell frequency is inversely correlated with the frequency of CD56(dim)CD16(+) NK cells in treatment-naive HIV-1 patients. Loss of CD56(dim)CD16(+) and expansion of CD56(-)CD16(+) NK cells again restore to the levels of healthy controls after ART. Enhanced immune activation of different NK cell subsets is partially restored after ART. Terminal differentiation of CD56(dim)CD16(+) NK cells is enhanced after ART as measured by CD57 expression. Frequencies of CD57(+)CD56(dim)CD16(+) NK cells are directly correlated with the frequencies of total NK cells suggesting that an increase in the frequencies of CD57(+)CD56(dim)CD16(+) NK cells is reflected by increased frequencies of total NK cells after ART. Taken together these data demonstrate that ART has an effect on the immune restoration of NK cells and is enhanced in the terminal differentiation of CD56(dim)CD16(+) NK cells, which is associated with increased frequencies of total NK cells after ART. SN - 1931-8405 UR - https://www.unboundmedicine.com/medline/citation/26352913/Terminal_Differentiation_of_CD56_dim_CD16_+__Natural_Killer_Cells_Is_Associated_with_Increase_in_Natural_Killer_Cell_Frequencies_After_Antiretroviral_Treatment_in_HIV_1_Infection_ L2 - https://www.liebertpub.com/doi/full/10.1089/aid.2015.0115?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -