Antiretroviral therapy partly reverses the systemic and mucosal distribution of NK cell subsets that is altered by SIVmac₂₅₁ infection of macaques.

We characterized three subsets of NK cells in blood, and two subsets in mucosal tissues. SIVmac251 infection increased total and CD16(+) NK cells in the blood. In the rectum, we observed a significant increase in total and NKG2A(+) NK cells during SIV infection. In contrast, the NKp44(+) subset significantly depleted in acute infection and continued to decline in frequency during chronic phase. During SIV infection, blood CD16 and mucosal NKG2A(+) subsets had increased cytotoxic potential. Intriguingly, the NKp44(+) NK cell subtype that likely mediates mucosal homeostasis via the production of cytokines, acquired cytotoxicity. Antiretroviral therapy significantly increased the frequency of mucosal NKG2A(+) NK cells and peripheral CD16(+) NK cells. However, it failed to restore the normal frequency of NKp44(+) NK cells in the rectum. Thus, SIVmac251 infection causes changes in the distribution and function of NK cells and antiretroviral therapy during chronic infection only partially restores NK homeostasis and function.