HIV-specific ADCC improves after antiretroviral therapy and correlates with normalization of the NK cell phenotype.
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.


METHODS
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.
*Virus Research and Development Laboratory, Department of Microbial Diagnostic and Virology, Statens Serum Institute, Copenhagen, Denmark; †Department of Infectious Diseases, Odense University Hospital, Odense, Denmark; and ‡Viro-immunology Research Unit, Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.
Sanne S
SS
Jensen
Hans J
HJ
Hartling
Jeanette L
JL
Tingstedt
Tine K
TK
Larsen
Susanne D
SD
Nielsen
Court
C
Pedersen
Anders
A
Fomsgaard
Ingrid
I
Karlsson
D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D054400:Receptors, CCR7 / Q000032:analysis; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis; D055815:Young Adult
D044966:Anti-Retroviral Agents; C515370:CCR7 protein, human; D015483:HIV Antibodies; D054400:Receptors, CCR7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7