HIV-specific ADCC improves after HAART and correlates with normalization of the NK cell phenotype

Sanne Skov JENSEN1,2, Hans Jakob HARTLING3, Jeanette Linnea TINGSTEDT1, Tine Kochendorf LARSEN1, Susanne Dam NIELSEN3, Court PEDERSEN2, Anders FOMSGAARD1,2 and Ingrid KARLSSON1
Affiliates: 1Virus Research & Development Laboratory, Department of Microbial Diagnostic and Virology, Statens Serum Institut, 2300 Copenhagen S, Denmark 2Department of Infectious Diseases, Odense University Hospital, 5000 Odense C, Denmark 3Viro-immunology Research Unit, Department of Infectious Diseases, Copenhagen University Hospital, 2100 Copenhagen Ø, Denmark

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Natural killer (NK) cell phenotype and function have recently gained much attention as playing crucial roles in antibody-dependent cellular cytotoxicity (ADCC). Within the context of HIV infection, the ability of NK cells to mediate ADCC may be critical for protection from disease acquisition and progression

We investigated NK cell function, as measured by ADCC, in HIV-1 positive individuals before and six months after highly active antiretroviral therapy (HAART) initiation. 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 were analyzed. The ADCC-GranToxiLux assay was used to evaluate the ability of NK cells and antibodies to mediate ADCC. The frequency of NK cells expressing receptors was determined by phenotypic labeling followed by flow cytometry.

The ability of NK cells to mediate ADCC was significantly increased after only six months of HAART and was not explained by a normalization of NK cell subsets but rather by a normalization of the NK cell phenotype. The frequency of NK cells expressing CCR7 and CD27 significantly decreased after six months of HAART. For individuals with no increase in ADCC after six months of HAART, the frequency of NK cells expressing NKp46 was down-regulated. The ability of antibodies to mediate ADCC alone and in combination in an autologous setup was not improved.

HAART improves the ability of NK cells to mediate ADCC after six months. This improvement does not correlate with general immune restoration, as measured by CD4+ T cell counts, but rather to a normalization of the NK cell phenotype. The investigation of the immune function during HAART is important in order to gain knowledge about who may respond to therapeutic vaccines.