Altered phenotype and function of NK cells infiltrating Human Papillomavirus (HPV)-associated genital warts during HIV infection

•Compared in vitro functional responses of NK and T cells in genital warts and blood.•HIV + women had significantly lower frequencies of CD4 T cells in genital warts.•CD4 T cells ability to produce IFNy did not differ between HIV + and HIV − women.•HIV + women had lower frequency of CD56Dim NK cells in both blood and warts.•NK cells from HIV + women expressed less CD107a or produced IFN-g after stimulation.

HIV-infected individuals experience more persistent HPV infections and are less likely to resolve genital warts. This study compared phenotype and functions of NK and T cells from genital warts and blood from 67 women. We compared in vitro functional responses of NK and T cells by multiparametric flow cytometry. HIV + women had significantly lower frequencies of CD4 T cells in warts (p = 0.001) and blood (p = 0.001). While the distribution of NK cell subsets was similar, HIV + women tended to have lower frequencies of CD56Dim NK cells in both blood (p = 0.0001) and warts (p = 0.006) than HIV − women. Wart NK cells from HIV + women expressed significantly lower CD107a and produced IFN-γ. HAART status was not associated with differences in NK cell functionality. We conclude that wart NK cells from HIV + women have defects in their ability to degranulate and/or secrete IFN-γ, which may provide insights into why HIV + women fail to spontaneously resolve genital warts.