CD56brightCD16- 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 CD56+/brightCD16dim/- expression is recently shown to present critical regulatory functions. Functional characteristics of CD56+/bright 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 CD56brightCD16- NK subset was significantly enriched in OA patients. These CD56brightCD16- 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 CD56brightCD16- NK cells from OA patients than in CD56brightCD16- NK cells from healthy controls. Also, the CD56brightCD16- 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 CD56brightCD16- NK cells were prone to express a higher level of IFNG, and the CD56brightCD16- NK cells from OA patients were more potent at stimulating IFNG than the CD56brightCD16- NK cells from healthy controls. Overall, our investigation demonstrated that CD56brightCD16- NK cells from osteoarthritis patients were shifted toward an IFN-γ-promoting phenotype and with reduced regulatory functions.