Anti-retroviral treatment of HIV infected individuals improves the ex vivo generation of memory-like NK cells

Abstract

The ability of Natural Killer (NK) cells, to generate memory-like responses against viruses including – HIV, opened up possibility of their application as immune therapy. We attempted to generate memory-like NK cells from HIV exposed and unexposed primary NK cells. The PBMCs of HIV uninfected and infected individuals (LTNPs, ART experienced and with progressive disease) were preactivated with cytokine cocktail (CC) of IL12, IL 15 and IL 18 with or without HIV-1 Env C or only IL 15 and restimulated with CC + HIV-1 Env C after seven days' rest. The CD56+ NK cells from the cultures were assessed for IFN-γ, TNF-α, and perforin secretion and expression of CD107a using multiparametric flow cytometry. Higher functionality was observed in case of pre-activation with CC with or without HIV-1 Env C as compared to only Il 15 across study groups. However, the functionality of the generated memory -like NK cells was significantly higher in case of LTNPs and the ART experienced individuals only. Low frequency of functional NK cells generated from HIV unexposed NK cells indicate probable specificity to HIV. The memory-like NK cells from ART experienced individuals generated after CC and CC+ HIV-1C preactivation showed good proliferating ability and also an ability to lyse the allogenic HIV infected CD4+ T cells. This work highlighted that HIV specific memory-like NK cells can be generated from the NK cells of HIV infected individuals with robust immune status after pre-activation with cytokine cocktail with or without HIV-1C. Although preliminary, these findings suggest that memory-like NK cells could have potential for use in immunotherapy aimed at clearing viral reservoirs.