ABSTRACT
Accumulating evidence has shown that allogeneic blood transfusions can induce significant immunosuppression in recipients, and thereby increase the risk of postoperative infection and/or tumor relapse. Although it is well known that natural killer (NK) cells are responsible for the immunodepression effects of transfusion, the underlying mechanisms remain obscure. In this study, we investigated the role of NK cells in transfusion-induced immunodepression in β-thalassemia major. The proportion of circulating NK cells and the expression of NK receptors (NKG2A, CD158a, NKP30, NKP46 and NKG2D) as well as CD107a were detected by multicolor flow cytometry. IFN-γ production by circulating NK cells was detected by intracellular cytokine staining. Our results showed that the proportion and cytotoxicity (CD107a expression) of circulating NK cells in transfusion-dependent β-thalassemia major patients were remarkably lower than those of β-thalassemia minor patients or healthy volunteers. Expression of NKG2A inhibitory receptor on circulating NK cells in patients with β-thalassemia major was remarkably up-regulated, but there were no significant differences in the expression levels of NKP30, NKP46, NKG2D, CD158a and IFN-γ. These results indicate NKG2A inhibitory receptor may play a key role in transfusion-induced immunodepression of NK cells in patients with β-thalassemia major.
Subject(s)
Adolescent , Child , Female , Humans , Male , Flow Cytometry , Gene Expression Regulation , Immunosuppression Therapy , Killer Cells, Natural , Allergy and Immunology , Metabolism , NK Cell Lectin-Like Receptor Subfamily C , Blood , Allergy and Immunology , NK Cell Lectin-Like Receptor Subfamily K , Blood , Allergy and Immunology , Natural Cytotoxicity Triggering Receptor 1 , Blood , Allergy and Immunology , Natural Cytotoxicity Triggering Receptor 3 , Blood , Allergy and Immunology , Receptors, KIR2DL1 , Blood , Allergy and Immunology , Transfusion Reaction , beta-Thalassemia , Blood , Allergy and Immunology , PathologyABSTRACT
<p><b>OBJECTIVE</b>To explore the mechanism of NK cell dysfunction in patients with multiple myeloma (MM).</p><p><b>METHODS</b>The expression of inhibitory receptors (CD158a and CD158b) and activating receptors NKG2D and NCRs (NKp30, NKp44 and NKp46) on CD3-CD56+NK cell of 13 MM patients and 30 healthy controls were analyzed by flow cytometry. The concentration of soluble NKG2D ligands (MICA, MICB, ULBP1, ULBP2 and ULBP3) in serum was detected by enzyme- linked immunosorbent assay (ELISA), and the cytotoxicity of NK cell against MM cell line by flow cytometry.</p><p><b>RESULTS</b>There are no significant differences of percentage and absolute number of NK cells, and the expression level of CD158a and CD158b between MM patients and healthy individuals (P>0.05). No NKp44 expression was detected on fresh isolated NK cells from both groups. There is no difference in inhibitor receptors expression between MM patients and healthy individuals but the expression of NKG2D, NKp30 and NKp46 on NK cells were higher in MM patients as compared with that in healthy individuals. The concentration of soluble NKG2D ligands in serum was higher in MM patients as compared with that in healthy individuals (P<0.05). Cultured healthy individual's NK cells with MM patient's serum could significantly decrease its cytotoxicity against MM cell line U266 cells [(38.5 ± 6.5) % vs (25.4 ± 5.9)%, P=0.044］.</p><p><b>CONCLUSION</b>The higher level of soluble NKG2D ligands in serum may be the mechanism of NK cell dysfunction in MM patient.</p>
Subject(s)
Humans , Cells, Cultured , Flow Cytometry , Killer Cells, Natural , Metabolism , Pathology , Multiple Myeloma , Allergy and Immunology , Metabolism , NK Cell Lectin-Like Receptor Subfamily K , Metabolism , Natural Cytotoxicity Triggering Receptor 1 , Metabolism , Natural Cytotoxicity Triggering Receptor 2 , Metabolism , Natural Cytotoxicity Triggering Receptor 3 , Metabolism , Receptors, KIR2DL1 , Metabolism , Receptors, KIR2DL3 , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the characteristics of inhibitory and activating receptor expressions on natural killer (NK) cells in HIV/HCV co-infected patients.</p><p><b>METHODS</b>Numbers, frequencies and expressions of activating and inhibitory receptors of NK cells were measured with flow cytometry (FCS) from HIV/HCV co-infected group (n = 24), HCV mono-infected group (n = 34), HIV mono-infected group (n = 21) and healthy control group (HC, n = 20), then analysis and compare were performed among those groups.</p><p><b>RESULTS</b>The NK cell absolute counts in HIV/HCV group were significantly lower than those in other three groups. The NKP30 and NKP46 frequencies on NK cells in HIV/HCV, HIV and HCV groups were all significantly lower than those in HC group, but there were no significant differences of NKP30 among former three groups; and NKP46 frequencies in HIV/HCV and HIV groups were lower than those in HCV group, but there were no significant differences between former two groups. The NKG2A frequencies in HIV/HCV and HCV groups were all higher than those in HIV and HC groups significantly, but the NKG2A frequencies in HIV group were lower than those in HC group; There were no significant differences of NKG2D, CD158a and CD158b among those four groups.</p><p><b>CONCLUSION</b>NK cell numbers and expressions of activiting receptors on NK cells obviously decreased in HIV/HCV co-infected patients, but some inhibitory receptors expressions increased, even higher than those of HIV mono-infected patients. NK cells impairments in HIV/HCV co-infection is more severe than HIV or HCV mono-infection.</p>