CD56CD16 natural killer cells are shifted toward an IFN-γ-promoting phenotype with reduced regulatory capacity in osteoarthritis.

A subset of natural killer (NK) cells with CD56CD16 expression is recently shown to present critical regulatory functions. Functional characteristics of CD56 NK cells in osteoarthritis (OA) patients remains unknown. Here, we remedied this problem by comparing the NK cells from healthy controls and OA patients. Data showed that the CD56CD16 NK subset was significantly enriched in OA patients. These CD56CD16 NK cells from OA patients presented significantly higher IFNG transcription and IFN-γ protein secretion than those from healthy controls, both directly ex vivo and after activation via various stimulating reagents, including IL-2/IL-15, K562, and PMA/ionomycin. On the other hand, the transcription and secretion of granzyme A (Gzm-A), Gzm-B, and perforin were significantly lower in CD56CD16 NK cells from OA patients than in CD56CD16 NK cells from healthy controls. Also, the CD56CD16 NK cells from OA patients were less capable of suppressing the proliferation of autologous CD4 T cells, in a manner that was dependent on the expression of Gzm-B and perforin. Interestingly, CD4 T cells co-incubated with CD56CD16 NK cells were prone to express a higher level of IFNG, and the CD56CD16 NK cells from OA patients were more potent at stimulating IFNG than the CD56CD16 NK cells from healthy controls. Overall, our investigation demonstrated that CD56CD16 NK cells from osteoarthritis patients were shifted toward an IFN-γ-promoting phenotype and with reduced regulatory functions.