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 six 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 (i.e. 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 six months of HAART and was not explained by a normalization of NK cell subsets (CD56CD16 and CD56CD16 NK cells) but rather by normalization in the frequency of NK cells expressing CCR7 and CD27. 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 model was not improved.
CONCLUSION:: 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 decrease in the frequency of NK cells expressing CCR7 and CD27.