NK cells of HIV-1-infected patients with poor CD4+ T-cell reconstitution despite suppressive HAART show reduced IFN-γ production and high frequency of autoreactive CD56bright cells

被引:13
作者
Giuliani, Erica [1 ]
Vassena, Lia [1 ]
Di Cesare, Silvia [1 ]
Malagnino, Vincenzo [2 ]
Desimio, Maria Giovanna [1 ]
Andreoni, Massimo [2 ]
Bamaba, Vincenzo [3 ,4 ]
Doria, Margherita [1 ]
机构
[1] Bambino Gesu Pediat Hosp, Lab Immunoinfectivol, IRCCS, Piazza S Onofrio 4, I-00165 Rome, Italy
[2] Tor Vergata Univ, Dept Med Syst, Via Montpellier 1, I-00133 Rome, Italy
[3] Sapienza Univ Roma, Dipartimento Med Interna & Specialita Med, Viale Policlin 155, I-00161 Rome, Italy
[4] Fdn Cenci Bolognetti, Ist Pasteur, Viale Policlin 155, I-00161 Rome, Italy
关键词
HIV-1; Immunological non-responders; CD56(bright) NK cells; Cytotoxicity; IFN-gamma; Treg cells; ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED PATIENTS; NATURAL-KILLER-CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; REGULATORY-CELLS; IMMUNOLOGICAL NONRESPONDERS; VIROLOGICAL RESPONSES; IMMUNE ACTIVATION; PERIPHERAL-BLOOD; THYMIC FUNCTION;
D O I
10.1016/j.imlet.2017.08.014
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
HIV-1-infected patients failing to recover CD4(+) T-cell count despite HAART (immunological non-responders, NRs), are at increased risk of disease progression and death. To better understand the NR status, we performed a comprehensive assessment of NK cells in NR patients as compared to immunologic responders. NRs exhibited an accumulation of CD56(bright) NK cells inversely correlated with CD4(+) counts. Both CD56(bright) and CD56(dim) NK cells of NRs displayed unimpaired degranulation ability, but poorly responded to cytokine stimulation in terms of NKp44 up-regulation and IFN-gamma production that may explain the susceptibility of NRs to infections and tumors. Notably, CD56(bright) NK cells from NRs showed higher cytotoxicity against autologous activated CD4(+) T cells. Moreover, NRs had reduced Treg cell counts that showed an inverse correlation with autoreactive CD56(bright) cells. These data suggest that accumulation of CD56(bright) NK cells, possibly linked to decreased homeostatic control by Tregs, contributes to poor immune reconstitution in NRs.
引用
收藏
页码:185 / 193
页数:9
相关论文
共 53 条
[1]   High CD56++CD16- natural killer (NK) cells among suboptimal immune responders after four years of suppressive antiretroviral therapy in an African adult HIV treatment cohort [J].
Bayigga, Lois ;
Nabatanzi, Rose ;
Sekiziyivu, Prossy Naluyima ;
Mayanja-Kizza, Harriet ;
Kamya, Moses R. ;
Kambugu, Andrew ;
Olobo, Joseph ;
Kiragga, Agnes ;
Kirimunda, Sam ;
Joloba, Moses ;
Nakanjako, Damalie .
BMC IMMUNOLOGY, 2014, 15
[2]   Mechanisms involved in the low-level regeneration of CD4+ cells in HIV-1-infected patients receiving highly active antiretroviral therapy who have prolonged undetectable plasma viral loads [J].
Benveniste, O ;
Flahault, A ;
Rollot, F ;
Elbim, C ;
Estaquier, J ;
Pédron, B ;
Duval, X ;
Dereuddre-Bosquet, N ;
Clayette, P ;
Sterkers, G ;
Simon, A ;
Ameisen, JC ;
Leport, C .
JOURNAL OF INFECTIOUS DISEASES, 2005, 191 (10) :1670-1679
[3]   CD56 negative NK cells: origin, function, and role in chronic viral disease [J].
Bjorkstrom, Niklas K. ;
Ljunggren, Hans-Gustaf ;
Sandberg, Johan K. .
TRENDS IN IMMUNOLOGY, 2010, 31 (11) :401-406
[4]   Antigen-activated human T lymphocytes express cell-surface NKG2D ligands via an ATM/ATR-dependent mechanism and become susceptible to autologous NK-cell lysis [J].
Cerboni, Cristina ;
Zingoni, Alessandra ;
Cippitelli, Marco ;
Piccoli, Mario ;
Frati, Luigi ;
Santoni, Angela .
BLOOD, 2007, 110 (02) :606-615
[5]   The biology of human natural killer-cell subsets [J].
Cooper, MA ;
Fehniger, TA ;
Caligiuri, MA .
TRENDS IN IMMUNOLOGY, 2001, 22 (11) :633-640
[6]   Naive T-cell depletion related to infection by X4 human immunodeficiency virus type 1 in poor immunological responders to highly active antiretroviral therapy [J].
Delobel, Pierre ;
Nugeyre, Marie-Therese ;
Cazabat, Michelle ;
Sandres-Saune, Karine ;
Pasquier, Christophe ;
Cuzin, Lise ;
Marchou, Bruno ;
Massip, Patrice ;
Cheynier, Remi ;
Barre-Sinoussi, Francoise ;
Izopet, Jacques ;
Israel, Nicole .
JOURNAL OF VIROLOGY, 2006, 80 (20) :10229-10236
[7]   NK cells in HIV infection: Paradigm for protection or targets for ambush [J].
Fauci, AS ;
Mavilio, D ;
Kottilil, S .
NATURE REVIEWS IMMUNOLOGY, 2005, 5 (11) :835-+
[8]   Regulatory T Cells in HIV-Infected Immunological Nonresponders Are Increased in Blood but Depleted in Lymphoid Tissue and Predict Immunological Reconstitution [J].
Gaardbo, Julie C. ;
Hartling, Hans J. ;
Ronit, Andreas ;
Springborg, Karoline ;
Gjerdrum, Lise M. R. ;
Ralfkir, Elisabeth ;
Thorsteinsson, Kristina ;
Ullum, Henrik ;
Andersen, Ase B. ;
Nielsen, Susanne D. .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2014, 66 (04) :349-357
[9]   Incomplete Immune Recovery in HIV Infection: Mechanisms, Relevance for Clinical Care, and Possible Solutions [J].
Gaardbo, Julie C. ;
Hartling, Hans J. ;
Gerstoft, Jan ;
Nielsen, Susanne D. .
CLINICAL & DEVELOPMENTAL IMMUNOLOGY, 2012,
[10]   IL-2-dependent adaptive control of NK cell homeostasis [J].
Gasteiger, Georg ;
Hemmers, Saskia ;
Bos, Paula D. ;
Sun, Joseph C. ;
Rudensky, Alexander Y. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2013, 210 (06) :1179-1187