Reference Intervals of Cytokeratin-19 Fragment (CYFRA 21-1) in Healthy Adults in China.

BACKGROUND: The reference intervals for serum cytokeratin-19 fragment (CYFRA 21-1) have not been established in Chinese population. This study aimed to measure serum CYFRA 21-1 levels in healthy Chinese subjects. METHODS: This cross-sectional, four-center study in two Chinese provinces enrolled participants (aged 18 - 85 years) with normal liver/kidney function and normal results for routine blood tests/urinalysis. Serum CYFRA 211 level was measured by ARCHITECT immunoassay (Abbott Diagnostics). RESULTS: The study included 3,366 participants. The median (interquartile range) value for serum CYFRA 21-1 level was 1.38 (1.00 - 1.89) ng/mL and tended to increase with age. The upper limit of the 97.5th percentile was 3.55 ng/mL and tended to increase with age. Serum CYFRA 21-1 median level varied between the four centers from 1.22 (0.89, 1.71) to 1.55 (1.12, 2.18) ng/mL, while the 97.5th percentile varied from 3.24 to 4.09 ng/mL. CYFRA 21-1 level correlated weakly with age and creatinine level. CONCLUSIONS: These new data can help to establish the 'normal range' of serum CYFRA 21-1 in people in China.

Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma.

Accumulating evidence shows that activity of the pyruvate kinase M2 (PKM2) isoform is closely related to tumorigenesis. In this study, we investigated the relationship between PKM2 expression, tumor invasion, and the prognosis of patients with lung adenocarcinoma. We retrospectively analyzed 65 cases of patients with lung adenocarcinoma who were divided into low and a high expression groups based on PKM2 immunohistochemical staining. High PKM2 expression was significantly associated with reduced patient survival. We used small interfering RNA (siRNA) technology to investigate the effect of targeted PKM2-knockout on tumor growth at the cellular level. In vitro, siRNA-mediated PKM2-knockdown significantly inhibited the proliferation, glucose uptake (25%), ATP generation (20%) and fatty acid synthesis of A549 cells, while the mitochondrial respiratory capacity of the cells increased (13%).Western blotting analysis showed that PKM2-knockout significantly inhibited the expression of the glucose transporter GLUT1 and ATP citrate lyase, which is critical for fatty acid synthesis. Further Western blotting analysis showed that PKM2-knockdown inhibited the expression of matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor (VEGF), which are important in degradation of the extracellular matrix and angiogenesis, respectively. These observations show that PKM2 activates both glycolysis and lipid synthesis, thereby regulating cell proliferation and invasion. This information is important in elucidating the mechanisms by which PKM2 influences the growth and metastasis of lung adenocarcinoma at the cellular and molecular level, thereby providing the basic data required for the development of PKM2-targeted gene therapy.

Formation and aggregation of lipid rafts in γδ T cells following stimulation with Mycobacterium tuberculosis antigens.

Lipid rafts are plasma membrane microdomains that are implicated in diverse signaling pathways in immune cells. Based on the distinct types of T-cell receptors, two T-cell subpopulations have been identified: αß and γδ T cells. In humans, γδ T cells represent a relatively rare T lymphocyte population but play a critical role in the immune response to infection by Mycobacterium tuberculosis. It has been demonstrated that Mycobacterium tuberculosis antigens (Mtb-Ag) preferentially activate γδ T cells. Thus, we investigated whether lipid rafts are involved in the Mtb-Ag-mediated activation of γδ T cells. Human peripheral blood mononuclear cells (PBMCs) were stimulated with Mtb-Ag, and expression of a lipid raft marker ganglioside GM1 (GM1) was determined by flow cytometry. The aggregation of lipid rafts was evaluated by laser confocal microscopy. Non-stimulated fresh PBMCs minimally expressed GM1 (6.55 ± 2.01%) and had no aggregated rafts in γδ T cells. Mtb-Ag stimulation gradually increased the expression of GM1 in a time-dependent manner. At 72 h, the majority of γδ T cells expressed GM1 (88.69 ± 7.55%). Furthermore, accompanied with the increased expression of GM1, aggregation of lipid rafts became gradually visible in γδ T cells. The aggregated rafts, however, were not evenly distributed and only occurred over a small portion of GM1-positive cells. Pretreatment with methyl-ß-cyclodextrin, a cholesterol-depleting reagent, completely inhibited the Mtb-Ag-mediated aggregation of lipid rafts. These results demonstrate that lipid raft aggregation occurs in Mtb-Ag-activated γδ T cells, suggesting that lipid rafts are involved in activation of γδ T cells.

Subcutaneous Administration of PDGF-AA Improves the Functional Recovery After Spinal Cord Injury.

Previous studies by our group have demonstrated that the transplantation of exogenous platelet-derived growth factor (PDGF)-AA-overexpressing oligodendrocyte progenitor cells (OPCs) promotes tissue repair and recovery of neurological function in a rat model of spinal cord injury (SCI). However, it remains unclear whether treatment with PDGF-AA also affects endogenous oligodendrocytes (OLs) or even neurons, thus promoting further functional recovery after SCI. In the present study, we evaluated the therapeutic potential of PDGF-AA treatment by direct subcutaneous injection of PDGF-AA immediately after SCI. We demonstrated that PDGF-AA injection resulted in increased tissue sparing, myelination and functional recovery in rats following SCI. Further experimentation confirmed that PDGF-AA increased the survival of endogenous OPCs and OLs, and promoted the proliferation of OPCs and their differentiation into OLs. Moreover, PDGF-AA also protected motor neurons from death in the injured spinal cord. These results indicated that PDGF-AA administration may be an effective treatment for SCI.

Quantitative assessment of HLA-DQ gene polymorphisms with the development of hepatitis B virus infection, clearance, liver cirrhosis, and hepatocellular carcinoma.

Hepatitis B is one of the most common infectious diseases, which leads to public health problems in the world, especially in Asian counties. In recent years, extensive human genetic association studies have been carried out to identify susceptible genes and genetic polymorphisms to understand the genetic contributions to the disease progression of HBV infection. HLA-DQ gene variations have been reported to be associated with HBV infection/clearance, disease progression and the development of hepatitis B-related complications, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC). However, the results are either inconclusive or controversial. Therefore, to derive a more precise estimation of the association, a meta-analysis was performed. Our data revealed that the HLA-DQ alleles rs2856718-G, rs7453920-A and rs9275319-G were significantly associated with decreased risk of HBV infection and HBV natural clearance. Logistic regression analyses showed that HLA-DQ alleles rs9275572-A significantly increased HBV infection clearance, and decreased HBV natural clearance. However, rs2856718-G and rs9275572-A were not associated with development of cirrhosis. The HLA-DQ polymorphisms (rs2856718 and rs9275572) were associated with a decreased HBV-related HCC risk in all genetic models, but rs9272105-A increased the risk of HBV-related HCC. In addition, no significant association was observed between HLA-DQ rs9275319-G polymorphism and HBV-related HCC. These stratified analyses were limited due to relatively modest size of correlational studies. In future, further investigation on a large population and different ethnicities are warranted. Our findings contribute to the personalized care and prognosis in hepatitis B.

Suppression of pyruvate dehydrogenase kinase-2 re-sensitizes paclitaxel-resistant human lung cancer cells to paclitaxel.

Despite impressive initial clinical responses, the majority of lung cancer patients treated with paclitaxel eventually develop resistance to the drug. Pyruvate dehydrogenase kinase-2 (PDK2) is a key regulator of glycolysis and oxidative phosphorylation, and its expression is increased in a variety of tumors. In this study, the role of PDK2 in mediating paclitaxel resistance in lung cancer cells was investigated using biochemical and isotopic tracing methods. Increased expression of PDK2 was observed in paclitaxel-resistant cells ascompared totheir parental cells. Down-regulation of PDK2 usingsiRNA increased the sensitivity to paclitaxel of resistant lung cancer cells. Targeting paclitaxel-resistant cells throughPDK2 knockdown was associated with reduced glycolysis rather than increased oxidative phosphorylation (OXPHOS). Moreover, combining paclitaxel withthe specific PDK2 inhibitor dichloroacetate had a synergistic inhibitory effect on the viability of paclitaxel-resistant lung cancer cells. These results indicate that paclitaxel-induced expression of PDK2 serves as an important mechanism for acquired paclitaxel resistance of lung cancer cells. They also highlight the importance of PDK2 for potential therapeutic interventions in patients who have developed a resistance to paclitaxel.

[Conditioned medium from rat RSC96 cells promotes proliferation of oligodendrocyte progenitor cells in vitro].

OBJECTIVE: To investigate the effect of conditioned medium from rat RSC96 cells (RSC96-CM) on the proliferation of oligodendrocyte progenitor cells (OPCs) and explore the underlying mechanism. METHODS: OPCs isolated from the spinal cords of SD rats of embryonic day 15 using immunopanning were treated with RSC96-CM. The proliferation of OPCs was detected using 5-bromo-2'-deoxyuridine (BrdU) incorporation assay. The mRNA expressions of PDGF-AA and bFGF in RSC96 cells were detected using RT-PCR, and their protein concentrations in RSC96-CM were detected with enzyme-linked immunosorbent assay (ELISA). The effects of PDGF-AA and bFGF in RSC96-CM on OPC proliferation and the roles of ERK and JNK signaling pathways in RSC96-CM-induced OPC proliferation were determined by application of their specific inhibitors. RESULTS: The percentage of BrdU+ OPCs was significantly increased in response to treatment with RSC96-CM (P<0.05), reaching the peak level when 50% RSC96-CM was added in the cell culture. RSC96 cells expressed a substantial amount of PDGF-AA and bFGF mRNAs, and PDGF-AA and bFGF protein concentrations in RSC96-CM were higher than those in a conditioned medium (B104CM) we used previously by 0.87 and 0.92 folds, respectively. Both the specific inhibitor of PDGFR signal pathway (AG1295) and the specific inhibitor of bFGFR signal pathway (PD173074) significantly attenuated RSC96-CM-induced OPC proliferation. The specific inhibitors of ERK signal pathway (U0126) and JNK signal pathway (SP600125) significantly decreased the percentage of BrdU+ cells in RSC96-CM-induced OPCs (P<0.01). CONCLUSION: RSC96-CM can effectively promote OPC proliferation, possibly as a result of PDGF-AA and bFGF secretion by RSC96 cells to activate ERK1/2 and JNK signaling pathways. RSC96- CM can be used as a routine stimulator for promoting OPC proliferation.

[Circulating levels of Th1- and Th2-chemokines increase in patients with early syphilis].

Objective To study the changes of plasma T helper type I (Th1)-and Th2-chemokine levels and analyze their roles in immune response and pathogenesis of early syphilis. Methods Heparin-anticoagulated peripheral blood was collected from 56 patients with early syphilis (primary syphilis, PS, n=22; secondary syphilis, SS, n=34) and healthy controls (HC, n=20). The levels of plasma Th1 chemokines including monokine induced by interferon-γ (MIG), interferon-γ inducible protein-10 (IP-10), interferon-inducible T-cell α chemoattractant (I-TAC) and Th2 chemokines including thymus-and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) were examined using ELISA. Meanwhile, the levels of plasma cytokines (IFN-γ, IL-4 and TNF-α) and C-reactive protein (CRP) were detected. Results The levels of plasma MIG, IP-10 and TARC, MDC in the patients with PS and SS were significantly higher than those in the healthy controls. Moreover, the level of I-TAC in the patients with SS was significantly higher than that in the healthy controls. In particular, the levels of plasma Th1 chemokines (MIG, IP-10 and I-TAC) in the patients with SS significantly increased compared with those with PS. However, no significant difference was observed in the levels of plasma Th2 chemokines (TARC and MDC) between the patients with PS and SS. The correlation analysis showed that there was an obvious positive correlation between IP-10 and MIG, I-TAC, IFN-γ, TNF-α levels in the patients with early syphilis. Furthermore, the levels of MIG and IP-10 were positively associated with plasma CRP in the patients with early syphilis. Conclusion Both Th1 chemokines and Th2 chemokines are involved in immune response of early syphilis.

[Analysis of Relationship between Serum Total Light Chain κ/λ Ratio and Proportion of Bone Marrow Plasma Cells in Patients with IgG type and IgA type Multiple Myeloma].

OBJECTIVE: To explore the relationship between serum total light chain κ/λ ratio (sTLC-κ/λ) and proportion of bone marrow plasma cells (BMPC) in patients with IgG type and IgA type multiple myeloma (MM) and its clinical significance. METHODS: The levels of serum IgG, IgA, κ type and λ type total light chain were detected in 79 newly diagnosed patients with IgG type (n=52) and IgA type (n=27) MM by immuno-nephelometric assay and the sTLC-κ/λ ratio was calculated. The proportion of BMPC was determined by bone marrow smears in the corresponding period, and the changes in sTLC-κ/λ ratio and the proportion of BMPC were observed in 19 patients with IgG type(n=16) and IgA type (n=3) MM undergoing treatment, 26 cases of non-phasmocytic proliferative diseases were enrolled in control group. RESULTS: In MM patients with IgGκ type and IgAκ type, the sTLC-κ/λ ratio was significantly higher than that in the control group (P<0.01), while in MM patients with IgGλ type and IgAλ type, the sTLC-κ/λ ratio was significantly lower than that in the control group (P<0.01). In MM patients with IgGκ, the sTLC-κ/λ ratio was significantly higher than that in MM patients with IgAκ(P<0.01), while the sTLC-κ/λ ratio in MM patients with IgGλ was significantly lower than that in MM patients with IgAλ. The sTLC-κ/λ ratios in MM patients with IgGκ and IgAκ were positively correlated with the concentrations of IgG (r=0.778,P=0.000) and IgA (r=0.601,P=0.039), while the sTLC-κ/λ ratios of patients with IgGλ and IgAλ were negativily correlated with the IgG(r=-0.586,P=0.01) and IgA level(r=-0.718,P=0.003). In addition, a correlation between each type MM was not found except the IgGκ type MM which had a positive correlation between the sTLC-κ/λ ratio and proportion of BMPC (r=0.579,P=0.002). Nonetheless, 18 of 19 patients with IgG type and IgA type MM undergoing treatment showed concordance between the sTLC-κ/λ ratio and proportion of BMPC change. CONCLUSION: There is a lower correlation between the sTLC-κ/λ ratio and the proportion of BMPC in MM patients with IgG type and IgA type, but there is a high concordance between the sTLC-κ/λ ratio and the proportion of BMPC change in the same patient and it suggests that the sTLC-κ/λ ratio plays an important role in the diagnosis and monitoring of IgG type and IgA type MM.

Meta-analysis of association between rs1447295 polymorphism and prostate cancer susceptibility.

AIMS: A number of studies have found that the single nucleotide polymorphisms (SNPs) within the 8q24 region of genome were associated with the susceptibility of prostate cancer. Association between 8q24 SNP variant rs1447295 and higher risk of prostate cancer had been investigated, but those studies were incomplete and the conclusions were obscure. METHODS: To better elucidate the relationship between rs1447295 polymorphism and the susceptibility of prostate cancer, we performed a more comprehensive meta-analysis about the association between rs1447295 polymorphism and prostate cancer susceptibility by collecting relevant articles published up to November, 2016 and excluding many replicated cohort data existing in previous reports, which made the conclusion more reliant and objective. RESULTS: The results showed that there was a significant prostate cancer risk associated with rs1447295 polymorphism not only in the total groups, but also in American, European and Asian descent subgroups. Meanwhile, a comprehensive analysis about the association between rs1447295 polymorphism and prostate cancer risk were conducted by using different clinical characteristic stratifications including Gleason score, tumor stage and PSA level. The result showed that rs1447295 polymorphism was correlated with different stages of prostate cancer. CONCLUSIONS: There are strong association between rs1447295 polymorphism and prostate cancer susceptibility in different ethnic groups and different prostate cancer stage, suggesting that rs1447295 might serve as a reliable biomarker for prostate cancer diagnosis.

Morroniside protects SK-N-SH human neuroblastoma cells against H2O2-induced damage.

Oxidative stress-induced cell injury has been linked to the pathogenesis of neurodegenerative disorders such as spinal cord injury, Parkinson's disease, and multiple sclerosis. Morroniside is an antioxidant derived from the Chinese herb Shan-Zhu-Yu. The present study investigated the neuroprotective effect of morroniside against hydrogen peroxide (H2O2)-induced cell death in SK-N-SH human neuroblastoma cells. H2O2 increased cell apoptosis, as determined by flow cytometry and Hoechst 33342 staining. This effect was reversed by pretreatment with morroniside at concentrations of 1-100 µM. The increase in intracellular reactive oxygen species (ROS) generation and lipid peroxidation induced by H2O2 was also abrogated by morroniside. H2O2 induced a reduction in mitochondrial membrane potential, increased caspase-3 activity, and caused downregulation of B cell lymphoma-2 (Bcl-2) and upregulation of Bcl-2-associated X protein (Bax) expression. These effects were blocked by morroniside pretreatment. Thus, morroniside protects human neuroblastoma cells against oxidative damage by inhibiting ROS production while suppressing Bax and stimulating Bcl-2 expression, thereby blocking mitochondrial-mediated apoptosis. These results indicate that morroniside has therapeutic potential for the prevention and treatment of neurodegenerative diseases.

Transplantation of PDGF-AA-Overexpressing Oligodendrocyte Precursor Cells Promotes Recovery in Rat Following Spinal Cord Injury.

Our previous study showed that Schwann cells (SCs) promote survival, proliferation and migration of co-transplanted oligodendrocyte progenitor cells (OPCs) and neurological recovery in rats with spinal cord injury (SCI). A subsequent in vitro study confirmed that SCs modulated OPC proliferation and migration by secreting platelet-derived growth factor (PDGF)-AA and fibroblast growth factor-2 (FGF)-2. We also found that PDGF-AA stimulated OPC proliferation and their differentiation into oligodendrocytes (OLs) at later stages. We therefore speculated that PDGF-AA administration can exert the same effect as SC co-transplantation in SCI repair. To test this hypothesis, in this study we investigated the effect of transplanting PDGF-AA-overexpressing OPCs in a rat model of SCI. We found that PDGF-AA overexpression in OPCs promoted their survival, proliferation, and migration and differentiation into OLs in vivo. OPCs overexpressing PDGF-AA were also associated with increased myelination and tissue repair after SCI, leading to the recovery of neurological function. These results indicate that PDGF-AA-overexpressing OPCs may be an effective treatment for SCI.

Differential effects of myelin basic protein-activated Th1 and Th2 cells on the local immune microenvironment of injured spinal cord.

Myelin basic protein (MBP) activated T cells (MBP-T) play an important role in the damage and repair process of the central nervous system (CNS). However, whether these cells play a beneficial or detrimental role is still a matter of debate. Although some studies showed that MBP-T cells are mainly helper T (Th) cells, their subtypes are still not very clear. One possible explanation for MBP-T immunization leading to conflicting results may be the different subtypes of T cells are responsible for distinct effects. In this study, the Th1 and Th2 type MBP-T cells (MBP-Th1 and -Th2) were polarized in vitro, and their effects on the local immune microenvironment and tissue repair of spinal cord injury (SCI) after adoptive immunization were investigated. In MBP-Th1 cell transferred rats, the high levels of pro-inflammatory cells (Th1 cells and M1 macrophages) and cytokines (IFN-γ, TNF-α, -ß, IL-1ß) were detected in the injured spinal cord; however, the anti-inflammatory cells (Th2 cells, regulatory T cells, and M2 macrophages) and cytokines (IL-4, -10, and -13) were found in MBP-Th2 cell transferred animals. MBP-Th2 cell transfer resulted in decreased lesion volume, increased myelination of axons, and preservation of neurons. This was accompanied by significant locomotor improvement. These results indicate that MBP-Th2 adoptive transfer has beneficial effects on the injured spinal cord, in which the increased number of Th2 cells may alter the local microenvironment from one primarily populated by Th1 and M1 cells to another dominated by Th2, Treg, and M2 cells and is conducive for SCI repair.

[Th2 differentiation features of Mycobacterium tuberculosis heat resistant antigen-activated human γδT cells and the regulation of transcription factor T-bet/GATA-3 on differentiation].

OBJECTIVE: To investigate Th2 differentiation features of Mycobacterium tuberculosis heat resistant antigens (MTB-HAg)-activated human γδT cells and the regulation of transcription factor T-box expression in T cells (T-bet) and GATA-binding protein 3 (GATA-3) on differentiation. METHODS: Peripheral blood mononuclear cells (PBMCs) were stimulated with MTB-HAg to generate MTB-HAg-activated T cells (MTBAT) and expanded in the neutral condition or Th2 polarizing condition. After restimulation for 6 hours with phorbol myristate acetate (PMA, 10 ng/mL), ionomycin (500 ng/mL) and monensin (2.5 µmol/L), intracellular cytokines (IFN-γ, IL-4) of γδT cells and αßT cells among MTBAT were detected by four-color fluorescence mAb staining combined with flow cytometry. The highly purified γδT cells and CD4⁺ T cells were sorted by flow cytometer from MTBAT that were cultured in neutral and Th2 polarizing conditions for 28 days. The expressions of T-bet and GATA-3 mRNA in purified γδT cells and CD4⁺ T cells were determined by reverse transcription PCR (RT-PCR) technique. RESULTS: γδT cells among MTBAT cultured in the neutral or Th2 polarizing condition predominantly produced IFN-γ, whereas the percentage of IFN-γ⁺ αßT cells significantly decreased in the Th2 polarizing condition as the culture time went by. Compared with the neutral condition, Th0 type (IFN-γ⁺ IL-4⁺) γδT cells significantly increased, and Th2 type (IFN-γ⁻ IL-4⁺) αßT cells also significantly increased in the Th2 polarizing condition. RT-PCR showed that mRNA expression of T-bet was still at a high level in γδT cells that were expanded in the Th2 polarizing condition, but at a low level in Th2 polarized CD4⁺ T cells. Moreover, the mRNA expressions of GATA-3 in both Th2 polarized γδT cells and CD4⁺T cells were up-regulated. CONCLUSION: In the Th2 polarizing condition, the majority of γδT cells in MTBAT still remained Th1 profile, whereas the portion of γδT cells differentiated into Th0 type cells. Both transcription factor T-bet and GATA-3 failed to display a fully cross-regulation function in Th2 polarized γδT cells.

Increased frequencies of Th17 and Th22 cells in the peripheral blood of patients with secondary syphilis.

T-helper (Th) 17 and the more recently identified Th22 cells are of great importance in host defense against pathogens, but can also be responsible for chronic inflammatory disorders. However, the roles of the two cell subsets in syphilis remain elusive. In this study, we show that the frequencies of Th17 and Th22 cells are significantly increased in the peripheral blood of patients with secondary syphilis (SS). A significant positive correlation is observed between Th17 and Th22 cells, whereas a negative correlation exists between Th17 and Th1 cells. Moreover, the frequency of Th17 cells has a significant positive correlation with the plasma interleukin 6 (IL-6) or IL-1ß levels, and the frequency of Th22 cells is positively correlated with the IL-6 or IL-23 levels. Finally, the elevated frequencies of Th17 and Th22 cells are positively associated with plasma C-reactive protein levels. Our results suggest that Th17 and Th22 cells may be implicated in the pathogenesis of the SS.

Lower concentrations of methyl-ß-cyclodextrin combined with interleukin-2 can preferentially induce activation and proliferation of natural killer cells in human peripheral blood.

Previous studies have demonstrated that high concentrations of methyl-ß-cyclodextrin (MßCD, 10-15 mM) can interfere with the formation of lipid rafts and inhibit activation of lymphocytes. In this report, we determined that lower concentrations of MßCD (1-4 mM) could accelerate the proliferation of lymphocytes in human peripheral blood mononuclear cells (PBMCs). In the expanded cells, CD3(-)CD56(+) natural killer (NK) cells were the dominant subpopulation, and a significant dose-effect relationship existed between the proportion of NK cells and the concentration of MßCD. In the groups treated with 3-4 mM MßCD, the proportions of NK cells reached a level of more than 60%. When PBMCs were treated with MßCD, CD69 was more preferentially expressed on CD3(-)CD56(+) cells than on CD3(+) cells at 48 and 72 hours. The expression of CD25 had no distinct difference at 48 hours, but when recombinant human interleukin-2 (IL-2) was added for a further 24 hours, it was also preferentially expressed on NK cells. MßCD and IL-2 synergistically could also induce interferon-γ (IFN-γ) production in CD56(+) human PBMCs. Mechanistic studies revealed that IFN-γ production in response to MßCD plus IL-2 was IL-12 independent but depended on endogenous IL-18 and IL-1ß, and CD56(+)CD14(+) dendritic cell-like cells and B cells might mediate the ability of MßCD to activate NK cells. The MßCD-activated NK cells also had high cytotoxicity against the natural killer cell-sensitive K562 cells or lymphokine-activated killer cell-sensitive DAUDI cells in vitro. These studies indicated that lower concentrations of MßCD combined with IL-2 can preferentially induce activation and proliferation of NK cells in PBMCs.