An NK Cell Population Lacking FcR gamma Is Expanded in Chronically Infected HIV Patients

作者：Zhou Jingling; Amran Fathiah S; Kramski Marit; Angelovich Tom A; Elliott Julian; Hearps Anna C; Price Patricia; Jaworowski Anthony^*

来源：The Journal of Immunology, 2015, 194(10): 4688-4697.

DOI：10.4049/jimmunol.1402448

We previously demonstrated that NK cells from HIV-infected individuals have elevated expression of activation markers, spontaneously degranulate ex vivo, and decrease expression of a signal-transducing protein for NK-activating receptors, FcR gamma. Importantly, these changes were maintained in virologically suppressed (VS) individuals receiving combination antiretroviral therapy (cART). In this study, we show that loss of FcR gamma is caused by the expansion of a novel subset of FcR gamma(-) CD56(dim) NK cells with an altered activation receptor repertoire and biological properties. In a cross-sectional study, FcR gamma(-) NK cells as a proportion of total CD56(dim) NK cells increased in cART-naive viremic HIV-infected individuals (median [interquartile range] = 25.9 [12.6- 56.1] compared with 3.80 [1.15-11.5] for HIV controls, p < 0.0001) and in VS HIV-infected individuals (22.7 [13.1-56.2] compared with 3.80 [1.15-11.5], p = 0.0004), with no difference between cART-naive and VS patients (p = 0.93). FcR gamma(-) NK cells expressed no NKp30 or NKp46. They showed greater Ab-dependent cellular cytotoxicity activity against rituximab-opsonized Raji cells and in a whole-blood assay measuring NK responses to overlapping HIV peptides, despite having reduced CD16 expression compared with conventional NK cells. Their prevalence correlated with CMV Ab titers in HIV- subjects but not in HIV+ individuals, and with the inflammatory marker CXCL10 in both groups. The expansion of a subset of NK cells that lacks NKp30 and NKp46 to similar to 90% of CD56(dim) NK cells in some VS HIV+ individuals may influence NK-mediated immunosurveillance in patients receiving cART.

• 出版日期2015-5-15