Platelet-monocyte cross talk and tissue factor expression in stable angina vs. unstable angina/non ST-elevation myocardial infarction

Tissue factor (TF), the major procoagulant in vivo, is usually absent from blood cells. However, since both monocyte TF (MoTF) expression and platelet activation are present in acute coronary syndrome we hypothesized that MoTF expression may in part depend on monocyte platelet aggregate (MPA) formation in coronary artery disease (CAD). Patients with unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI, n?=?20) had significantly higher levels of MoTF (17.4?±?3.1MFI) and MPAs (CD42b:273?±?183MFI; CD62P:256.3?±?48.5MFI) than patients with stable angina (SA, n?=?40; MoTF:13.2?±?2.2MFI, p?=?0.001; CD42b:160?±?113MFI, p?=?0.025; CD62P:118.7?±?24.5MFI, p?=?0.018) as measured by whole blood flow cytometry on CD14+-cells. TF-activity of isolated mononuclear cells (MNC) was elevated in UA/NSTEMI (75?±?27?pg/mL) in comparison to SA (47?±?17?pg/mL, p?=?0.001) as determined by chromogenic assay, and TF mRNA expression in isolated MNC was more frequent in UA/NSTEMI than in SA (50% vs. 18.2%; p?=?0.017). MoTF expression significantly correlated with the constitutive platelet marker CD42b (r?=?0.69, p?相似文献   

MAdCAM-1 does not play a central role in the early pathophysiology of autoimmune hepatitis

IntroductionCD4+ T cells are thought to have a central role in the pathogenesis of autoimmune hepatitis (AIH). Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) directs homing of CD4+ T cells in the alimentary tract and is a therapeutic target in inflammatory bowel diseases. Here we assessed MAdCAM-1 expression in AIH and viral hepatitis and related its expression with immune infiltrate analysis and histopathological key features.MethodsHepatic portal areas of pretreatment biopsies (n=10) and follow-up biopsies (n=9) of patients with a confirmed diagnosis of AIH were assessed for MAdCAM-1 expression and infiltrate composition using immunohistochemistry and multispectral imaging (Vectra® Polaris?). Controls consisted of biopsies of patients with untreated chronic viral hepatitis B or C (n=22).ResultsMAdCAM-1 expression on endothelium was sparsely present in portal fields of two treatment-naïve AIH patients. Three patients showed MAdCAM-1 expression within lymphoid aggregates. No expression of significance (including single-cell expression) was observed in the remaining 6 patients. In contrast, viral hepatitis C biopsies showed endothelial MAdCAM-1 expression in 8 of 13 untreated patients. Densities of both B-cells (CD20+) and CD4+ T-cells (CD3+ CD8-) were increased in AIH and viral hepatitis patients with MAdCAM-1 expression.ConclusionMAdCAM-1 was detected in liver biopsies in a minority of patients with AIH at the time of diagnosis suggesting no central role in its pathophysiology. Lymphoid or reticular MAdCAM-1 pattern expression was associated with more dense infiltrates of both B-cells and CD4⁺ T-cells, and may be related to the formation of secondary lymphoid follicles.     

Over-expression of RPL23 in myelodysplastic syndromes is associated with apoptosis resistance of CD34+ cells and predicts poor prognosis and distinct response to CHG chemotherapy or decitabine

Ribosomal protein (RP) L23 has been suggested to be a negative regulator of cell apoptosis. In the present study, we analyzed RPL23 expression in 169 patients with myelodysplastic syndrome (MDS) by using real-time PCR. The apoptosis of CD34(+) marrow cells was examined by flow cytometry, and the correlation between RPL23 expression levels and apoptosis in CD34(+) cells was assessed. We then analyzed the clinical significance of RPL23 expression for predicting disease progression and patient survival as well as therapeutic response in patients administered with a cytarabine, homoharringtonine, and G-CSF (CHG) regimen or decitabine therapy. Increased RPL23 expression was found in patients with higher-risk MDS than in patients with lower-risk disease (p?=?0.004). RPL23 expression levels were found being inversely correlated with decreased apoptotic ratio of CD34(+) cells in higher-risk patients (r?=?-0.672, p?相似文献   

Adipocytes modulate the electrophysiology of atrial myocytes: implications in obesity-induced atrial fibrillation

Obesity is an important risk factor for atrial fibrillation (AF). Increased epicardial adipose tissue in obesity can enhance inflammation and plays an important role in the pathophysiology of AF. However, it is not clear whether epicardial adipocytes directly modulate the electrophysiological characteristics of atrial myocytes. Whole-cell patch clamp was used to record the action potentials (APs) and ionic currents in isolated rabbit left atrium (LA) myocytes incubated with and without (control) isolated adipocytes from epicardial, retrosternal, or abdominal adipose tissues, or adipocytes-conditioned supernatant for 2-4?h. Compared to control LA myocytes (n?=?22), LA myocytes incubated with epicardial (n?=?17), retrosternal (n?=?18), or abdominal adipocytes (n?=?22) had longer (80?±?3, 109?±?6, 109?±?6, and 110?±?7?ms, p??0.05) in comparison to control myocytes. Epicardial adipocyte-incubated LA myocytes had larger late sodium currents, L-type calcium currents, and transient outward potassium currents, but smaller delayed rectifier potassium and inward rectifier potassium currents than control LA myocytes. Moreover, isoproterenol (10?nM) induced a higher incidence (67 vs. 22?%, p?相似文献   

Changes in immune cell frequencies after cyclophosphamide or mycophenolate mofetil treatments in patients with systemic lupus erythematosus

This study was designed to explore the profile of immune cell subsets, including T, B, natural killer (NK), and NKT cells, in systemic lupus erythematosus (SLE) patients, and to determine their relationships with the clinical index and the effects of cyclophosphamide (CYC) and mycophenolate mofetil (MMF) treatment. SLE patients (n?=?28) and age/sex-matched healthy controls (n?=?28) were evaluated. The patients were equally divided into two treatment groups: intravenous drip (IVD) with CYC and prednisolone, and oral MMF and IVD with prednisolone. SLE peripheral blood samples were taken immediately prior to treatment and after 4?weeks of drug treatment. T, B, NK, and NKT cell subsets were measured by flow cytometry. Double-stranded DNA antibody and Sm antibody were detected by indirect immunofluorescence. Serum C3, C4, and C-reactive protein were determined by scatter turbidimetry. The percentages of CD3+CD4+ T, CD3-CD16CD56+ NK, and CD3+CD16CD56+ NKT cells and the CD4+/CD8+ ratio were significantly lower in SLE patients, while CD3+CD8+ T and CD3-CD19+ B cells were higher than the controls. The lymphocyte subsets were significantly correlated with the SLE disease activity index (SLEDAI) and complement factors (C3, C4). Four weeks of CYC or MMF treatment led to a significant increase in CD3+CD4+ T cells (P?相似文献   

Impaired regulatory T cell reconstitution in patients with acute graft-versus-host disease and cytomegalovirus infection after allogeneic bone marrow transplantation

To elucidate the correlation between regulatory T cells (Tregs) and acute graft-versus-host disease (aGVHD) or cytomegalovirus infection following allogeneic bone marrow transplantation (allo-BMT), we evaluated either CD4?CD25(high) or FOXP3? Treg-enriched cells in peripheral blood (PB) from 20 patients who received allo-BMT, and in biopsies of skin with aGVHD. Proportions of CD4?CD25(high)FOXP3? cells in total lymphocytes, but not other types of T cells, were lower in patients who eventually developed grades II-IV aGVHD (n = 13) than in others (n = 7, P < 0.001). Proportions of CD62L? cells in CD4?CD25(high) cells at day +30 were lower (P < 0.01) in patients who eventually showed cytomegalovirus viremia (n = 6) than in others (n = 14). Incidence of aGVHD (P < 0.05) or cytomegalovirus viremia (P < 0.05) was higher in patients without these complications, but with lower proportions of PB CD4?CD25(high)FOXP3? cells at day +30 (n = 8) than in others (n = 8). However, in skin with aGVHD (n = 5), there was marked or slightly increased infiltration of CD8? cells (P < 0.001) or CD3?FOXP3? cells (P < 0.05), respectively, when compared with control (n = 5), resulting in threefold higher ratio of CD8?/CD3?FOXP3? cells in aGVHD relative to controls (P < 0.05). Thus, impaired reconstitution of Tregs may be associated with aGVHD and CMV infection. Moreover, imbalance of Tregs and CD8? cells may play a role in aGVHD tissue.     

T cells bearing gamma/delta T cell receptor and their expression of activation antigen in peripheral blood from patients with Sj?gren's syndrome.

T cells bearing gamma/delta T cell receptor (gamma/delta + T cells) and their expression of activation antigen (HLA-DR) or the marker of natural killer (NK) cells (CD56), were examined in the peripheral blood lymphocytes (PBL) from twenty-two patients with Sj?gren's syndrome (SS) by three-color flowcytometry to elucidate possible pathological roles of the T cell subset in SS. The frequency of gamma/delta + T cells in PBL was not elevated in SS patients, while that of gamma/delta - T cells, which are T cells bearing the alpha/beta T cell receptor (alpha/beta + T cells), was significantly low in the patients, as compared with 22 healthy controls. We found that the proportions of activated cells (HLA-DR+) in both the gamma/delta + and alpha/beta+T cell subsets were significantly higher in the patients than in the controls. The proportions of HLA-DR+ cells in cells in both patients and controls. Furthermore, the frequency of activated cells in both T cell subsets correlated with the duration of disease in SS patients. However, no difference was found in the percentages of total CD56+ cells, CD56+CD3- cells (true NK cells), CD56+CD3+T cells, CD56+gamma/delta+T cells, or CD56-gamma/delta+T cells between the patients and controls. The above results indicate that immunologic activation in SS patients is progressive and involves both alpha/beta+ and gamma/delta+ T cell subsets.     

Reduced apoptosis of CD8+ T-lymphocytes in the airways of smokers with mild/moderate COPD

Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation in airways and lung parenchyma. CD8+ T-lymphocytes, crucial effector and regulatory cells in inflammation, are increased in the central and peripheral airways in COPD. The aim of this study was to assess the role of apoptosis in the accumulation of CD8+ T-lymphocytes within the airway wall in COPD. We examined the submucosa of transverse sections of central and peripheral airways from post-operative tissues from non-smokers (n?=?16), smokers with normal lung function (n?=?16), smokers with mild/moderate COPD (n?=?16), and smokers with severe/very severe COPD (n?=?9). TUNEL and immunohistochemistry techniques were used to identify apoptosis and cell phenotype, respectively. The percentage of apoptotic CD8+ T-lymphocytes was significantly lower (p?相似文献   

A possible role for CCL27/CTACK-CCR10 interaction in recruiting CD4 T cells to skin in human graft-versus-host disease

Graft-versus-host disease (GvHD) is a serious complication of allogeneic stem cell transplantation (SCT) affecting the skin, gut and liver. The involvement of distinct organs suggests a role for tissue-specific chemokines and their receptors in directing activated donor T cells to these sites. In this study the potential involvement of the skin-specific CCL27/CTACK-CCR10 interaction was investigated in 15 paediatric SCT patients with skin GvHD. During the course of skin GvHD, peripheral blood T cells from these patients contained a high proportion of CD4+ CCR10+ T cells that disappeared after the GvHD was resolved. These cells were CD45RO+, expressed additional skin homing markers (cutaneous lymphocyte-associated antigen and CCR4), and produced the T-cell helper type 1-cytokines tumour necrosis factor-alpha and interleukin-2. The increase in CD4+ CCR10+ T cells was absent in SCT patients without GvHD. Immunohistochemical investigations showed CD4+ CCR10+ T cells in the GvHD skin biopsies of the same patients, but not in the gut biopsies of patients also suffering from gut GvHD. The infiltration of CD4+ CCR10+ T cells in the GvHD-affected skin correlated with an enhanced epidermal expression of CCL27/CTACK, the ligand for CCR10. These findings support the involvement of CCL27/CTACK-CCR10 interaction in recruiting CD4+ T cells to the skin, thus contributing to the pathogenesis of acute GvHD.     

Immunohistological analysis of synovial tissue for differential diagnosis in early arthritis.

OBJECTIVE: An early diagnosis in patients presenting with arthritis is important to provide information about prognosis and to initiate treatment. The objective of this study was to determine which markers applied in immunohistological analysis of synovial tissue (ST) specimens could be used to differentiate rheumatoid arthritis (RA) from other forms of arthritis. METHODS: Synovial biopsies were obtained by blind needle techniques from 95 patients with early arthritis. After follow-up of at least 2 yr to verify the diagnosis, the patients could be classified as follows: RA (n=36), undifferentiated arthritis (UA; n=21), osteoarthritis (OA; n=17), reactive arthritis (ReA; n=10), ankylosing spondylitis (AS; n=3), psoriatic arthritis (PsA; n=2) and crystal-induced arthritis (CA; n=6). ST sections were analysed by immunohistochemistry using monoclonal antibodies against CD3, CD4, CD8, CD22 (B cells), CD38 (plasma cells), CD68 (macrophages) and CD55 (fibroblast-like synoviocytes). RESULTS: Logistic regression analysis revealed that the higher scores for the numbers of CD38+ plasma cells and CD22+ B cells in RA were the best discriminating markers comparing RA to non-RA patients (CD38: P=0.0001; CD22: P<0.05). Polychotomous regression analysis comparing three diagnostic categories (1: RA; 2: UA, ReA, AS and PsA; 3: OA and CA) also identified the score for the number of CD38+ plasma cells (P<0.0001) as well as the numbers of CD68+ macrophages in the synovial sublining (P=0.05) as discriminating markers. CONCLUSION: The results suggest that immunohistochemical analysis of ST specimens from early arthritis patients can be used to differentiate RA from non-RA patients. The numbers of plasma cells, B cells and macrophages are especially increased in ST of patients with RA. Future studies in early arthritis patients with clinical features which do not allow an immediate confident diagnosis may clarify the role of this test system in differential diagnosis.     

Association of PTPN22 gene (rs2488457) polymorphism with ulcerative colitis and high levels of PTPN22 mRNA in ulcerative colitis

Purpose

Our aims were to evaluate protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene polymorphisms in ulcerative colitis (UC) and explore PTPN22 mRNA levels in colonic biopsies of UC patients in central China.

Methods

A total of 165 Chinese UC patients and 300 healthy controls were enrolled in this study. PTPN22 ?1123G/C, +1858C/T, and +788G/A polymorphisms were genotyped by PCR-restriction fragment length polymorphism method. PTPN22 mRNA expressions in colonic biopsies and serum C-reactive protein (CRP) levels were determined by quantitative PCR and immunonephelometry, respectively.

Results

The frequency of C carrier was higher in UC patients than in healthy controls (66.7 vs. 53.3 %, P?=?0.005, odds ratios?=?1.75, 95 % CI 1.18–2.60) and associated with extensive colitis (P?=?0.029). PTPN22 mRNA levels were elevated in UC patients than in healthy controls (P?<?0.001). Among UC patients, PTPN22 mRNA expression levels were higher in biopsies of inflamed colonic tissue compared with noninflamed tissue (P?<?0.001) and were correlated with CRP levels (r?=?0.578, P?<?0.001). PTPN22 mRNA expression levels were elevated in extensive colitis compared to proctitis (P?=?0.008) and to left-sided colitis (P?=?0.029) and were higher in moderate and severe disease than in mild disease (P?=?0.005).

Conclusions

Our study showed the potential association between PTPN22 ?1123G/C polymorphism and UC in central China. PTPN22 mRNA levels were highly expressed in UC, especially in active disease, and were correlated with CRP levels, disease location, and disease severity in UC patients.     

A histomorphometric analysis of synovial biopsies from individuals with Gulf War Veterans’ Illness and joint pain compared to normal and osteoarthritis synovium

We compared histologic, immunohistochemical, and vascular findings in synovial biopsies from individuals with Gulf War Veterans Illness and joint pain (GWVI) to findings in normal and osteoarthritis (OA) synovium. The following parameters were assessed in synovial biopsies from ten individuals with GWVI: lining thickness, histologic synovitis score, and vascular density in hematoxylin & eosin-stained sections; and CD68+ lining surface cells and CD15+, CD3+, CD8+, CD20+, CD38+, CD68+, and Ki-67+ subintimal cells and von Willebrand Factor+ vessels immunohistochemically. Comparisons were made to synovial specimens from healthy volunteers (n = 10) and patients with OA or RA (n = 25 each). Histologic appearance and quantitative assessments were nearly identical in the GWVI and normal specimens. Vascular density was between 25% (H & E stains; p = 0.003) and 31% (vWF immunostains; p = 0.02) lower in GWVI and normal specimens than in OA. CD68+ macrophages were the most common inflammatory cells in GWVI (45.3 +/- 10.1 SEM cells/mm(2)) and normal synovium (45.6 +/- 7.4) followed by CD3+ T cells (GWVI, 15.1 +/- 6.3; normal, 27.1 +/- 9.2), whereas there were practically no CD20+, CD38+, and CD15+ cells. All parameters except lining thickness and CD15 and CD20 expression were significantly higher in OA. Five (20%) OA specimens contained significant fractions of humoral immune cells in mononuclear infiltrates, although the overall differences in the relative composition of the OA mononuclear infiltrates did not reach statistical significance compared to GWVI and normal synovium. In summary, the GWVI and normal synovia were indistinguishable from each other and contained similar low-grade inflammatory cell populations consisting almost entirely of macrophages and T cells.     

Hematopoietic stem cell mobilization with the reversible CXCR4 receptor inhibitor plerixafor (AMD3100)��Polish compassionate use experience

Recent developments in the field of targeted therapy have led to the discovery of a new drug, plerixafor, that is a specific inhibitor of the CXCR4 receptor. Plerixafor acts in concert with granulocyte colony-stimulating factor (G-CSF) to increase the number of stem cells circulating in the peripheral blood (PB). Therefore, it has been applied in the field of hematopoietic stem cell mobilization. We analyzed retrospectively data regarding stem cell mobilization with plerixafor in a cohort of 61 patients suffering from multiple myeloma (N?=?23), non-Hodgkin's lymphoma (N?=?20), or Hodgkin's lymphoma (N?=?18). At least one previous mobilization attempt had failed in 83.6% of these patients, whereas 16.4% were predicted to be poor mobilizers. The median number of CD34+ cells in the PB after the first administration of plerixafor was 22/μL (range of 0-121). In total, 85.2% of the patients proceeded to cell collection, and a median of two (range of 0-4) aphereses were performed. A minimum of 2.0?×?10(6) CD34+ cells per kilogram of the patient's body weight (cells/kg b.w.) was collected from 65.6% of patients, and the median number of cells collected was 2.67?×?10(6) CD34+ cells/kg b.w. (0-8.0). Of the patients, 55.7% had already undergone autologous stem cell transplantation, and the median time to neutrophil and platelet reconstitution was 12 and 14?days, respectively. Cases of late graft failure were not observed. We identified the diagnosis of non-Hodgkin's lymphoma and previous radiotherapy as independent factors that contributed to failure of mobilization. The current report demonstrates the satisfactory efficacy of plerixafor plus G-CSF for stem cell mobilization in heavily pre-treated poor or predicted poor mobilizers.     

Cytokine flexibility of early and differentiated memory T helper cells in juvenile idiopathic arthritis

OBJECTIVE: It has been suggested that CD45RO+CD27+ T cells represent recently activated memory cells, whereas CD45RO+CD27- T cells are activated memory T cells in the process of differentiating into effector cells. We investigated (1) CCR7 and CCR5 expression and (2) modulation of cytokine expression in "early" (CD27+) and "differentiated" (CD27-) memory CD4+ T cells from peripheral blood and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA). METHODS: SF CD4+CD45RO+CD27+ and CD27- memory T cells from 6 patients with JIA were tested by flow cytometry for intracellular interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) after in vitro priming with CD3 and CD28 mAb in the presence of IL-4, and subsequent culture with IL-2. RESULTS: SF CD4+CD45RO+CD27+ cells contained higher proportions of CCR7+ (median 46% vs 23%) and lower proportions of CCR5+ (73% vs 90%) cells than paired CD27- T cells. Both CD27+ and CD27- memory T helper cells from SF displayed a higher IFN-gamma/IL-4 ratio than their peripheral blood counterparts. No significant difference was observed in the percentage of IFN-gamma-expressing cells between CD27+ (32%, range 4-47%) and CD27- (29.4%, range 5-52%) memory T helper cells from SF. CONCLUSION: Irrespective of their differentiation stage, both CD27+ and CD27- SF memory T helper cells were found to switch from a proinflammatory to an antiinflammatory pattern of cytokine production.     

The mobilization of CD34 positive mononuclear cells after myocardial infarction is abolished by revascularization of the culprit vessel

BACKGROUND: The mobilization of hematopoietic progenitor cells from bone marrow has been proposed to play a role in cardiac regeneration after myocardial infarction (MI). Accordingly, an increase in CD34 positive cells (CD34+) has been observed in the peripheral blood of patients after acute myocardial infarction. Here, we evaluated the influence of an acute percutaneous coronary intervention (PCI) of the occluded artery on the mobilization of CD34+ in acute MI. METHODS: CD34 positive cells were quantified by flow cytometry (FACS analysis) and expressed as number per million white blood cells. Peripheral blood was obtained and analyzed at day 5 after the onset of symptoms from patients with acute MI without early PCI (n=11, age 63+/-5 years), acute MI with rapid PCI (n=7, age 63+/-3), patients with pneumonia (n=5, age 51+/-6), patients without angiographical signs of coronary artery disease (control, n=5, age 66+/-8) and young healthy volunteers (n=11, age 28+/-1). RESULTS: Patients with MI but without PCI had a higher CD34+ count at day 5 (312+/-48 per 10(6) leukocytes) than control (156+/-40, P=0.03) and MI with PCI (173+/-31, P=0.03). No increase in CD34+ was observed in patients who underwent PCI vs. control. Patients with pneumonia had higher CD34+ (350+/-44) than patients with MI with PCI (P=0.01) and control (P=0.01). Healthy individuals who were much younger than all other groups (28+/-1 years, P<0.0001 vs. all groups) had the highest CD34+ (526+/-51, P=0.006 vs. MI without PCI, P=0.00003 vs. MI with PCI, P=0.02 vs. pneumonia, P=0.00006 vs. control). CONCLUSIONS: Shorter time of ischemia and reduced cell death may be the reasons for reduced CD34+ cell count after acute MI with early percutaneous intervention vs. acute MI without intervention. Besides ischemia, also inflammation as present in pneumonia may cause a mobilization of CD34+ cells. Age may be a major factor that influences the mobilization of CD34+ cells and the regenerative capacity of the heart.     

Increased HLA-G Expression in Tissue-Infiltrating Cells in Inflammatory Bowel Diseases

Background

Since HLA-G is an immune checkpoint molecule and since Crohn’s disease (CD) and ulcerative colitis (UC) exhibit deregulated immune-mediated mechanisms, we aimed to evaluate intestinal HLA-G expression and soluble HLA-G (sHLA-G) levels in CD/UC patients stratified according to the CD phenotype/localization and UC extension.

Methods

HLA-G tissue expression was assessed by immunohistochemistry in biopsies collected from 151 patients (90 CD, 61 UC) and in surgical resection specimens (28 CD, 12 UC). Surgical material from 24 healthy controls was also assessed. Plasma sHLA-G levels (97 CD, 81 UC, and 120 controls) were evaluated using ELISA.

Results

HLA-G expression was similarly observed in the intestinal epithelial cells of control and CD/UC specimens. However, in biopsies, the plasma cells/lymphocytes infiltrating the lamina propria in CD/UC presented (1) increased HLA-G expression compared to controls (P?<?0.0001), (2) greater cell staining in UC cells than in CD cells irrespective of disease extent (P?=?0.0011), and (3) an increased number of infiltrating cells in the inflammatory CD phenotype compared to that in the stenosing and fistulizing phenotypes (P?=?0.0407). In surgical specimens, CD/UC patients exhibited higher infiltrating cell HLA-G expression in lesion areas than in margins. sHLA-G levels were higher in UC/CD patients (P?<?0.0001) than in controls, but no difference was observed between diseases.

Conclusions

Increased infiltrating cell HLA-G expression associated with increased sHLA-G levels in CD/UC patients may reflect ongoing host strategies to suppress chronic inflammation.

     

Papillary thyroid carcinomas from young adults and children contain a mixture of lymphocytes

The immune response appears to be important in preventing metastasis and recurrence of thyroid cancer. We previously showed that papillary thyroid carcinoma (PTC) from children and adolescents that contain the most numerous proliferating lymphocytes have the best prognosis. However, the types of lymphocytes involved are not yet known. To further define this, we examined 21 PTCs from patients 21 yr of age or younger (52% were 18-21 yr of age) for the presence of CD4+ (helper), CD8+ (killer), CD19+ (B cells), and CD56+ (natural killer) cells as well as proliferating lymphocytes (Ki-67+). Nearly half the PTCs contained CD4+ (9 of 21, 43%), CD8+ (8 of 21, 38%), or CD19+ (10 of 21, 48%) lymphocytes. Only one PTC (1 of 21, 5%) contained CD56+ lymphocytes, and none contained all four cell types. By dual staining, none of these lymphocytes were proliferating (Ki-67+). However, PTCs containing either CD8+ cells (n = 8) or a combination of CD4+, CD8+, and CD19+ cells (n = 5) contained more numerous proliferating lymphocytes than did PTCs containing any other combination (14.2-fold increase, P = 0.03 and 13.1-fold increase, P = 0.003, respectively). During follow-up, none of the PTCs containing either CD8+ lymphocytes or the combination of CD4+, CD8+, and CD19+ lymphocytes recurred. However, the cohort is too small and the follow-up inadequate to provide accurate information on the clinical impact of these immunological findings. We conclude that the immune response against PTC is important and also complex, involving more than one type of lymphocyte.     

Natural killer cell activity influences outcome after T cell depleted stem cell transplantation from matched unrelated and haploidentical donors

Lytic activity and recovery of natural killer (NK) cells was monitored in pediatric patients with leukemias (ALL, AML, CML, JMML) and myelodysplastic syndromes after transplantation of T cell depleted stem cells from matched unrelated (n?=?18) and mismatched related (haploidentical, n?=?29) donors. CD34?+?selection with magnetic microbeads resulted in 8?×?10(3)/kg residual T cells. No post-transplant immune suppression was given. NK cells recovered rapidly after transplantation (300 CD56+/μL at day 30, median), whereas T cell recovery was delayed (median: 12 CD3+/μL at day 90). NK activity was measured as specific lysis of K 562 targets several times (mean: 3 assays per patient). Four temporal patterns of lytic activity could be differentiated: consistently low, consistently high, decreasing and increasing activity. Patients with consistently high or increasing activity had significantly lower relapse probability than patients with consistently low or decreasing levels (0.18 vs 0.73 at 2 years, p?相似文献   

Clinicopathological and prognostic characteristics of CD56-negative multiple myeloma

We analysed CD56 expression in 70 patients with multiple myeloma (MM) to determine its clinicopathological and prognostic significance. Fifty-five (79%) patients were CD56+. CD56- patients (n = 15) had higher beta2 microglobulin levels and a higher incidence of extramedullary disease, Bence Jones protein, renal insufficiency and thrombocytopenia than CD56+ patients. Their myelomas more frequently had a plasmablastic morphology. Overall survival was significantly lower in CD56- than CD56+ patients (22 vs 63 months, P = 0.0002). We conclude that CD56- MM is a discrete entity associated with more aggressive disease. The higher incidence of plasmablastic cases suggested that CD56- MM may develop from a less mature plasma cell than CD56+ MM.     

Leukemic burden in subpopulations of CD34+ cells isolated from the mobilized peripheral blood of alpha-interferon-resistant or -intolerant patients with chronic myeloid leukemia

We attempted to determine the frequency of normal hematopoietic stem cells (HSC) and contaminating leukemic cells in mobilized peripheral blood (MPB) collected from chronic myeloid leukemia (CML) patients, intolerant of alpha-interferon or with interferon-resistant disease. A total of 14 MPB samples, six from patients in chronic phase (CP) and eight from patients in accelerated phase or blast crisis (AP/BC) were studied. Cytogenetic analysis of MPB collected from AP/BC patients showed that 100% of the cells were Ph+, whereas cells from four of five CP MPB were Ph-. By contrast, fluorescence in situ hybridization (FISH) analysis of CP MPB showed a mean frequency of 14.7% Ph+ cells, while AP/BC MPB contained 39.2% Ph+ cells. In an attempt to purify normal HSC, subpopulations of the MPB CD34+ cells were isolated based on expression of the Thy-1 antigen (CDw90). The mean Ph+ cell frequency as determined by FISH within the CD34+Thy-1+Lin- and CD34+Thy-1-Lin- populations from CP patients was 19.2% and 33.9%, respectively. In the AP/BC patients, levels of residual leukemic cells were significantly greater with mean Ph+ cell frequencies of 59.2% and 72.7% for the CD34+Thy-1+Lin- and CD34+Thy-1-Lin- fractions, respectively. The frequency of cobblestone area forming cells (CAFC) was used as a means of quantitating the numbers of functional HSC within these cell subpopulations. The mean CAFC frequency was 1 of 19 for the CD34+Thy- 1+Lin- cells as compared with 1 of 133 for the Thy-1-fraction indicating a higher frequency of primitive progenitor cells in the Thy- 1+ subpopulation. CD34+ cell subsets from two patients were also injected into SCID-hu bone assays to determine the in vivo behavior of these cell populations. After 8 weeks, multilineage donor engraftment was observed in these grafts. FISH analysis of the donor cells within the grafts showed that 55.3% and 60.0% of the cells were Ph+. We conclude that unfractionated MPB from this patient population is not leukemia-free and that the CD34+Thy-1+Lin- cell subpopulation, although predominantly enriched for normal HSC, still contains substantial numbers of residual leukemic cells.