title: Increased Natural Killer Cell Activation in HIV-Infected Immunologic Non-Responders Correlates with CD4+ T Cell Recovery after Antiretroviral Therapy and Viral Suppression.
abstract: The role of natural killer (NK) cell function in HIV disease especially in the setting of long-term antiretroviral therapy (ART) and viral suppression is not fully understood. In the current study, we have investigated NK cell activation in healthy controls and aviremic ART-treated HIV+ subjects with different degrees of immune restoration. We performed a cross sectional study in 12 healthy controls and 24 aviremic ART-treated HIV-infected subjects including 13 HIV+ subjects with CD4+ T cells above 500 cells/μL defined as "immunologic responders" and 11 HIV+ subjects with CD4+ T cells below 350 cells/μL defined as "immunologic non-responders". We analyzed NK cell number, subset, and activation by expression of CD107a and NKG2D and co-expression of CD38 and HLA-DR. NK cell-mediated cytotoxicity against uninfected CD4+ T cells was tested in vitro. We found that NK cell absolute number, percentage of NK cells, and percentage of NK cell subsets were similar in the three study groups. The increased NK cell activation was found predominantly in CD56dimCD16+ subset of immunologic non-responders but not immunologic responders compared to healthy controls. The activation of NK cells was inversely correlated with the peripheral CD4+ T cell count in HIV+ subjects, even after controlling for chronic T cell activation, sex, and age, potential contributors for CD4+ T cell counts in HIV disease. Interestingly, NK cells from immunologic non-responders mediated cytotoxicity against uninfected CD4+ T cells ex vivo. NK cells may play a role in blunted CD4+ T cell recovery in ART-treated HIV disease.
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, United States of America.
authors.forename: Zhenwu
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, United States of America.|Beijing You'an Hospital, Capital Medical University, No.8 Xitoutiao, You'an men wai, Fengtai District, Beijing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Divison of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: Martin
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, United States of America.|Department of Infectious Disease, the Second Affiliated Hospital of the Southeast University, Nanjing, China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Beijing You'an Hospital, Capital Medical University, No.8 Xitoutiao, You'an men wai, Fengtai District, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, United States of America.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Divison of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Kilby
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heath
authors.affiliation: The 302 Hospital of PLA, Treatment and Research Center for Infectious Diseases, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, United States of America.|Divison of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis / Q000276:immunology; D000328:Adult; D000367:Age Factors; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000096:biosynthesis / Q000276:immunology; D012737:Sex Factors
chemical_list: D044966:Anti-Retroviral Agents; C527085:KLRK1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; D008562:Membrane Glycoproteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1