TY - JOUR
T1 - HIV-specific ADCC improves after antiretroviral therapy and correlates with normalization of the NK cell phenotype
AU - Jensen, Sanne Skov
AU - Hartling, Hans Jakob
AU - Tingstedt, Jeanette Linnea
AU - Larsen, Tine
AU - Nielsen, Susanne Dam
AU - Pedersen, Court
AU - Fomsgaard, Anders
AU - Karlsson, Ingrid
PY - 2015/2/1
Y1 - 2015/2/1
N2 - BACKGROUND: Natural killer (NK) cell phenotype and function have recently gained much attention as playing crucial roles in antibody-dependent cellular cytotoxicity (ADCC). We investigated NK cell function, as measured by ADCC, in HIV-1-positive individuals before and 6 months after highly active antiretroviral therapy (HAART) initiation.METHOD: The ability of antibodies and NK cells to mediate ADCC was investigated separately and in combination in an autologous model. The NK cell subset distribution and NK cell phenotype (ie, expression of maturation and activation markers within NK cell subsets) were analyzed.RESULTS: The ability of NK cells to mediate ADCC was significantly increased after only 6 months of HAART and was not explained by a normalization of NK cell subsets (CD56 CD16 and CD56 CD16 NK cells) but rather by normalization in the frequency of NK cells expressing CCR7 and CD27. For individuals with no increase in ADCC after 6 months of HAART, the frequency of NK cells expressing NKp46 was downregulated. The ability of antibodies to mediate ADCC alone and in combination in an autologous model was not improved.CONCLUSIONS: HAART improves the ability of NK cells to mediate ADCC after 6 months. This improvement does not correlate with general immune restoration, as measured by CD4 T-cell counts, but rather to a decrease in the frequency of NK cells expressing CCR7 and CD27.
AB - BACKGROUND: Natural killer (NK) cell phenotype and function have recently gained much attention as playing crucial roles in antibody-dependent cellular cytotoxicity (ADCC). We investigated NK cell function, as measured by ADCC, in HIV-1-positive individuals before and 6 months after highly active antiretroviral therapy (HAART) initiation.METHOD: The ability of antibodies and NK cells to mediate ADCC was investigated separately and in combination in an autologous model. The NK cell subset distribution and NK cell phenotype (ie, expression of maturation and activation markers within NK cell subsets) were analyzed.RESULTS: The ability of NK cells to mediate ADCC was significantly increased after only 6 months of HAART and was not explained by a normalization of NK cell subsets (CD56 CD16 and CD56 CD16 NK cells) but rather by normalization in the frequency of NK cells expressing CCR7 and CD27. For individuals with no increase in ADCC after 6 months of HAART, the frequency of NK cells expressing NKp46 was downregulated. The ability of antibodies to mediate ADCC alone and in combination in an autologous model was not improved.CONCLUSIONS: HAART improves the ability of NK cells to mediate ADCC after 6 months. This improvement does not correlate with general immune restoration, as measured by CD4 T-cell counts, but rather to a decrease in the frequency of NK cells expressing CCR7 and CD27.
KW - NK cell phenotype
KW - NK cell subsets
KW - Natural killer cell
KW - antibody-dependent cellular cytotoxicity
KW - antiretroviral therapy
KW - Killer Cells, Natural/chemistry
KW - Antibody-Dependent Cell Cytotoxicity
KW - HIV Antibodies/immunology
KW - Humans
KW - Middle Aged
KW - Immunophenotyping
KW - Male
KW - Receptors, CCR7/analysis
KW - Tumor Necrosis Factor Receptor Superfamily, Member 7/analysis
KW - Anti-Retroviral Agents/therapeutic use
KW - HIV Infections/drug therapy
KW - Young Adult
KW - Adult
KW - Female
KW - Aged
KW - Longitudinal Studies
U2 - 10.1097/QAI.0000000000000429
DO - 10.1097/QAI.0000000000000429
M3 - Journal article
C2 - 25394194
VL - 68
SP - 103
EP - 111
JO - J A I D S
JF - J A I D S
SN - 1525-4135
IS - 2
ER -