Activating natural killer receptors in behcet's disease

Behcet's disease (BD) is a chronic inflammatory disease with unknown ethiology, which is characterized by relapse and remission periods. Immunologic abnormalities triggered by environmental factors in genetically susceptible subjects underlyes BD. Natural Killer Receptors (NKR) expressed on innate and adaptive immune cells could initiate or amplify immune responses that can bridge these two arms. In this study, Peripheric Blood Mononuclear Cells (PBMC) isolated from BD patients (remission n=7, activation n=7) and healty subjects (n=6) were stimulated with IL-12, IL-15, IL-18 and IL-23 in various combinations. NKG2D, NKp30, NKp46, CD69+ and IL-12RB2+ expression on CD4+, CD8+, CD16+ cells were investigated. Proliferation capacity, cytotoxic activity and CD107a expression were determined by using flow cytometry. In this study, increased CD69 expression on CD4 and CD8 T cells in remission group, in comparison with active patients were observed in unstimulated condition. Expression of CD8+NKp46+ cells were higher in remission group when compared with both active patients and controls, in unstimulated condition. CD107a expression was diminished in active group when compared with control group. In K562 stimulated lymphocytes, diminished CD07a levels were observed in remission group in comparison with healthy controls. Cytokine combinations including IL-12+IL-15, IL-18+IL-15 and IL-23+IL-15, significantly increased proliferative capacity of CD3-CD56+ and CD3+ cells of Behcet's patients when compared with healthy subjects. Our study suggests that in T cells CD69 and IL-15 may play a role in the pathogenesis of BD due to effects on both CD3+ T and CD3- NK cells