Up-regulation of NKG2A inhibitory receptor on circulating NK cells contributes to transfusion-induced immunodepression in patients with β-thalassemia major / 华中科技大学学报（医学）（英德文版）

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.

Analysis of risk factors associated to cytomegalovirus infection in dentistry students / Análisis de factores de riesgo asociados a la infección por citomegalovirus en estudiantes de odontología

The purpose of the study was to analyze the association between cytomegalovirus (CMV) infection in dental students with occupational risk factors and a genetic trait (NKG2C gene deletion). Study design: Case-control study. 176 students were included and divided in two groups according to CMV serological results: those with CMV infection (case group) and those without prior infection (control group). Demographic, occupational, and the presence of NKG2C gene deletion were compared between both groups. Results: The presence of CMV IgG antibodies was detected in 104 (59.1 percent) students (case group) while 72 (40.9 percent) students were CMV negative (control group). The frequency of patient contact, the use of protective barriers, and the number of reported accidents was compared between the study groups; no significant differences were noted. The appropriate use of infection-control measures was observed in the majority of students in both study groups. In the case group the frequency of NKG2C deletion was 9.7 percent compared to 5.6 percent in the control group (p=0.33). Conclusion: No association between the presence of CMV infection with occupational and genetic risk factors was found in this population. Dentists should be aware of the CMV prevalence and risks factors associated to this infection, particularly among child-bearing age dentist women...

El objetivo de este estudio fue analizar la asociación entre la infección por citomegalovirus (CMV) en estudiantes de odontología con factores de riesgo ocupacionales y un polimorfismo genético (deleción del gen NKG2C). Diseño del Estudio: Estudio de casos y controles. 176 estudiantes fueron incluidos y divididos en dos grupos de acuerdo al resultado serológico para CMV: aquellos con la infección por CMV (grupo de casos) y aquellos que no presentaron infección por CMV (grupo control). Las características demográficas, ocupacionales y la presencia de la deleción del gen NKG2C fueron comparadas entre ambos grupos. Resultados: La presencia de anticuerpos IgG de CMV fue detectada en 104 (59.1 por ciento) estudiantes (grupo de casos) mientras que 72 (40.9 por ciento) estudiantes fueron negativos a CMV (grupo control). Se comparó la frecuencia de contacto con el paciente, el uso de barreras protectoras y el número de accidentes ocupacionales reportados entre los grupos de estudio. No fueron detectadas diferencias significativas. El uso apropiado de las medidas de control de infección fue observado en la mayoría de los estudiantes de ambos grupos. En el grupo de casos la frecuencia de la deleción de NKG2C observada fue de 9.7 por ciento comparada con un 5.6 por ciento en el grupo control (p=0.33). Conclusión: No se encontró asociación entre la infección por CMV con los factores de riesgo ocupacionales y genéticos de esta población. Los dentistas deben conocer la frecuencia de la infección por CMV, así como los factores de riesgo asociados, particularmente las mujeres odontólogas en edad fértil...

The studies for activating and inhibitory receptors on natural killer cells in HIV/HCV co-infected patients / 中华实验和临床病毒学杂志

<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>

Expression of NKG2D and NKG2A with their ligands MHC-I A/B and HLA-E in acute leukemia patients and its significance / 中国实验血液学杂志

This study was aimed to explore the difference of NK cell receptor NKG2D and NKG2A expression on NK cells and CD3(+) T cells and their ligand MHC-I A/B (major histocompatibility complex class I-related chains A/B) and HLA-E expression in leukemia cells, as well as its immunological significance. Flow cytometry was used to detect the killing rate of NK92 cells to 8 leukemia cell lines, and the expression of NKG2D and NKG2A on NK cells and CD3(+) T cells as well as their ligand MHC-I A/B and HLA-E expression on leukemia cells. The results indicated that the NK92 showed different killing activity to different leukemia cell lines. The positive expression rate of NKG2D and NKG2A on NK cells and CD3(+) T cells in ALL patients was no significantly different from that in AML patients (p > 0.05), but positive expression rate of MHC-I A/B and HLA-E in ALL patients was obviously higher than that in AML patients (p < 0.05). It is concluded that there is difference of immune cell function between ALL and AML patients, this difference may be associated with the expression difference of NKG2D and NKG2A ligands on leukemia cells while does not associated with the killing and inhibiting receptors expressed on NK cells and CD3(+) T cells.

Study on expression of natural killer (NK) cell C-type lectin-like receptors in nasal NK/T-cell lymphomas / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression and possible role of C-type lectin-like natural killer cell receptors, including CD94 and NKG2s, in extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT).</p><p><b>METHODS</b>Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of CD94 and NKG2s in tissue sections of 21 cases of EN-NK/T-NT(confirmed by histology, immunohistochemistry, in-situ hybridization for Epstein-Barr virus(EBV) and PCR for T-cell receptor genes), eight midline B cell lymphomas (BCL), 10 peripheral T cell lymphoma of lymph nodes (PTCL), five spleens, five thymuses and five chronic nasopharyngitis.</p><p><b>RESULTS</b>All 21 cases of EN-NK/T-NT showed typical histological features, with expression of CD3epsilon, CD56, cytotoxic granules and positivity of EBV in 20 cases. The RT-PCR results showed a high level expression of CD94 (85.7%) and NKG2 members (95.2% totally, with NKG2A/2B in 85.7%, NKG2D in 61.9%, NKG2F in 14.3%, NKG2C/2E in 4.8%, respectively and sequentially) in EN-NK/T-NT. But in the controls, none of the receptors were detected in TCL (0%) and BCL (0%), while only a few cases of lymphoid tissues expressed one or two of these receptors (two spleens and two chronic nasopharyngitis mucosa for CD94, one spleen for NKG2A/2B and one thymus for NKG2D). The differences of CD94 and NKG2 expression between EN-NK/T-NT and BCL or TCL were statistically significant (P<0.01). Co-expression of CD94 and NKG2 was found in 17 out of 21 EN-NK/T-NT cases (81.0%).</p><p><b>CONCLUSIONS</b>The specific and sequential expression nature of CD94 and NKG2 in EN-NK/T-NT, mimics the developmental expression model in their normal counterparts, and suggests that the tumor cells of most cases are being activated and keeping in a stage as the functional NK cells. Detection of these molecules may provide a useful tool to confirm the diagnosis of NK cell lymphoma.</p>

Comparison of the quantities and subset distributions of natural killer cells among different races / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Natural killer (NK) cells play critical roles in host immune defense, while the quantities and subset distributions may vary among different races. To address the difference, we compared these variables among Chinese Han, the Caucasians and the Blacks. The study may provide critical background information for both basic research and clinical investigation.</p><p><b>METHODS</b>Blood samples collected from populations of different races were tested within 12 hours after collection and subsets of NK cells were characterized using flow cytometry.</p><p><b>RESULTS</b>The absolute NK count in the Chinese Han was significantly higher than that in the Caucasian. The Han and Caucasian groups showed higher percentages of cytotoxic subset compared to that of the Black group. The percentage of cytokine-producing subset of Chinese Han group was lower than that of Caucasian and Black groups. Black group had a higher percentage of function-unknown NK subset than that of the Han and Caucasian groups.</p><p><b>CONCLUSION</b>Our data indicated that NK cell count and the distribution of different subsets varied among different races, which should be taken into consideration in related investigations.</p>

Identification of a novel candidate gene KLRC1 within the putative susceptibility locus for systemic lupus erythematosus at 12p12.3-13.2 in a Chinese cohort / 南方医科大学学报

<p><b>OBJECTIVE</b>To identify the candidate genes within the putative susceptibility locus for systemic lupus erythematosus (SLE) at 12p12.3-13.2.</p><p><b>METHODS</b>KLRC1 was selected as the candidate gene according to the results of previous gene chip studies. TaqMan real-time quantitative PCR was performed for detecting KLRC1 mRNA expression in 55 SLE patients and 30 controls.</p><p><b>RESULTS AND CONCLUSION</b>KLRC1 mRNA expression was significantly higher in the mononuclear cells and T cells of SLE patients than in the healthy controls (P<0.01), but showed no significant difference in the B cells. No obvious correlation was found between the SLE disease activity index (SLEDAI) and KLRC1expression level, suggesting that KLRC1 can be a probable candidate gene for SLE on 12p12.3-13.2, but which is not associated with the disease activity.</p>

The negative regulatory effect of IFN-gamma on cognitive function of human natural killer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the regulatory effect of IFN-gamma on recognition of target cells by human natural killer (NK) cells.</p><p><b>METHODS</b>The cytotoxic activity of human NK cell lines (NK92, NKL) was detected by MTT method. Expression of NK cell receptors (NKG2D, NKG2A/B, KIR2DL1 and KIR2DS1) and MICA on target cells (the ligand of NKG2D) was measured by RT-PCR.</p><p><b>RESULTS</b>Both NK92 and NKL cells exerted higher cytotoxicity to tumor cells with MICA expression, while tumors without MICA expression could resist NK cell lysis. IFN-gamma (> 1000 U/ml) inhibited NK lysis of tumor cells with MICA expression through down-regulating the expression of NKG2D, but up-regulating the expression of NKG2A/B and KIR2DL1.</p><p><b>CONCLUSION</b>IFN-gamma has a negative effect on activation and cytotoxicity of human NK cells by altering the balance between the expression of activating and inhibitory receptors on NK cells in favor of inhibition. This may serve to limit NK cell over-activation in vivo.</p>

NK cell receptors and related ligands / 中国医学科学院学报

NK cell has antigen-non-specific receptors on its surface. Based on the molecular structure, NK cell receptors can be divided into two types, including Ig superfamily and C-type lectin superfamily. Based on function, NK cell receptors can be divided into activation receptors (NKAR) and inhibition receptors (NKIR). NKAR includes CD16 mediating antibody dependent cytotoxicity, NKR-P1 mediating natural cytotoxicity, KAR conjugated with DAP12 and co-stimulatory receptor. They transduce signal through the ITAM motif in their cytoplasmic region. NKIR mainly include KIR and CD94/NKG2. Their ligands are MHC-I molecules. They are closely related to the recognition of auto cells by NK cells. Inhibition of NKAR activation and cytotoxic effect of NK cells by NKIR are carried out through the ITIM motif and require co-aggregation of NKAR and NKIR.

CD94/NKG2A--a kind of inhibitory receptor belonging to C-type lectin superfamily / 中国医学科学院学报

CD94/NKG2A is a kind of inhibitory receptor belonging to C-type lectin superfamily. It specifically expresses on the surface of some lymphocytes such as NK cells and T cells, and mediates inhibitory signal. In this mini-review, the structure of CD94/NKG2A molecule is described and its biological significance is discussed.