ABSTRACT
OBJECTIVE@#To explore the expression characteristics of antigens and functional markers of natural killer (NK) cells in patients with acute myeloid leukemia (AML).@*METHODS@#Multi-parameter flow cytometry was used to detect NK cell surface markers and their functional indicators in 56 newly diagnosed AML patients and 24 healthy controls, including activating receptors NKG2D, NKP46, DNAM-1, and killing indicators granzyme B, perforin.@*RESULTS@#Referring to the WHO hematopoiesis and lymph tissue tumor classification criteria, 56 cases were roughly divided into three types: AML M1, M2, and M4/M5. However, there was no differences about NK cells among the three types, so it was no longer subdivided. NK cells were divided into two groups: CD3-CD56hiCD16- (CD56hiNK) and CD3-CD56dimCD16+ (CD56dimNK). Compared with CD56dimNK cell population, except for NKP46, the positive expression levels of NKG2D and other receptors of CD56hiNK cells in AML patients decreased (P<0.001). Compared with healthy controls, the proportion of CD56hiNK cells in AML patients increased, while the number and proportion of NK cells and proportion of CD56dimNK cells significantly decreased (P<0.05). The proportion of perforin in CD56hiNK cells significantly increased (P<0.05). The expression of DNAM-1 in CD56hiNK cells, NKG2D, DNAM-1, and perforin in CD56dimNK cells decreased significantly (P<0.05). There was no statistically significant difference in expression of other functional indexes in AML patients compared with corresponding indexes of healthy controls. In addition, the proportion of CD56hiNK cells was positively correlated with the expression of CD34+ in AML (r=0.303).@*CONCLUSION@#Compared with CD56dimNK, the ratio of CD56hiNK and the expression of functional markers in AML patients are lower. Compared with healthy controls, the number and expression ratio of NK cells in AML patients decrease and the expression of functional markers is abnormal, indicating that its function is impaired.
Subject(s)
Humans , CD56 Antigen , Flow Cytometry , Killer Cells, Natural , Leukemia, Myeloid, AcuteABSTRACT
Objective: To investigate the killing effect of amplified natural killer (NK) cells on the gastric cancer cells, and to elucidate its mechanism. Methods: The peripheral blood mononuclear cells (PBMCs) from 15 patients with gastric cancer were extracted and isolated. The morphology of NK cells before and after amplification was observed, the percentages of NK cells before and after amplification were detected, and the amplification time of NK cells after amplification was calculated. The killing effects of NK cells on the gastric cancer cells before and after amplification were detected. The percentages of expressions of killing activating receptors NKG2D and DNAM-1 and killing inhibitory receptors KIR2DL1 and KIR3DL1 were detected by flow cytometry. Results: Before amplification, the NK cells were round, small in size and scattered in distribution. After amplification, the NK cells were increased in size and irregular in shape. The percentage of NK cells after amplification was significantly higher than that before amplification ( P<.0. 01). and the number of the NK cells after amplification was (596 ± 152) times of before amplification. When the effective target ratio was 5 : 1. the killing activity of NK cells on the gastric cancer cells after amplification was significantly higher than that before amplification (P<0.01). After amplification, the percentages of expressions of killing activating receptors NKG2D and DNAM-1 were significantly higher than those before amplification ( P<0. 01). After amplification, the percentages of expressions of killing inhibitory receptors KIR2DL1 and KIR3DL1 were significantly lower than those before amplification (P<0.05). Conclusion: The killing effect of NK cells on the gastric cancer cells after amplification is stronger than before amplification. The mechanism may be related to increasing the expressions of activated receptors and decreasing the expressions of inhibitory receptors on the surface of NK cells after amplification.
ABSTRACT
Natural killer (NK) cells play a pivotal role in early surveillance against virus infection and cellular transformation, and are also implicated in the control of inflammatory response through their effector functions of direct lysis of target cells and cytokine secretion. NK cell activation toward target cell is determined by the net balance of signals transmitted from diverse activating and inhibitory receptors. A distinct feature of NK cell activation is that stimulation of resting NK cells with single activating receptor on its own cannot mount natural cytotoxicity. Instead, specific pairs of co-activation receptors are required to unleash NK cell activation via synergy-dependent mechanism. Because each co-activation receptor uses distinct signaling modules, NK cell synergy relies on the integration of such disparate signals. This explains why the study of the mechanism underlying NK cell synergy is important and necessary. Recent studies revealed that NK cell synergy depends on the integration of complementary signals converged at a critical checkpoint element but not on simple amplification of the individual signaling to overcome intrinsic activation threshold. This review focuses on the signaling events during NK cells activation and recent advances in the study of NK cell synergy.
Subject(s)
Killer Cells, Natural , VirusesABSTRACT
Activating and inhibitory cell surface receptors play important roles in regulation of immune responses. Recent progress has demonstrated that many inhibitory receptors pair with activating, as well as inhibitory, isoforms, both of whose genes are located in small clusters on a chromosome. We and others identified paired activating and inhibitory immunoglobulin-like receptors, designated myeloid-associated immunoglobulin-like receptors (MAIR) (CD300). MAIR is a multigene family consisting of nine genes on a small segment of mouse chromosome 11. MAIR family receptors are preferentially expressed on myeloid cells, including macrophages, dendritic cells, granulocytes, and bone-marrow-derived cultured mast cells, and a subset of B cells and regulate activation of these cells. Thus, MAIR plays an important role in innate immunity mediated by myeloid cells.