CD66 expression in acute leukaemia

Antibodies against CD66 identify antigens from the carcinoembryonic antigen (CEA) family of proteins, which belong to the immunoglobulin gene superfamily. Despite being usually restricted to cells of myeloid or monocytic origin, CD66 expression has also been reported in blasts from children with B-cell lineage acute lymphocytic leukaemia (ALL). An analysis of the CD66 expression was undertaken in a series of acute leukaemia patients. Antigenic expression was analysed using triple combinations of monoclonal antibodies (mAbs) in forty-five patients. The CD66 Kat4 fluorescein isothiocyanate clone was purchased from Dako (Glostrup, Denmark). CD66 was expressed in 2 of 29 patients with AML (acute myeloblastic leukemia) (6.8%) and in 8 of 12 patients with B-cell lineage ALL (66.7%; P <0.001); in blast crisis (BC) of chronic myelocytic leukaemia (CML), CD66 was expressed in two patients with lymphoid BC but not in the two with myeloid BC. The co-expression of CD66 with other myeloid antigens was observed in all CD66+ ALL/Ly-BC cases tested: CD 13 in six patients, CD33 in seven and CD117 in two patients. The CD66 expression is more frequent in ALL than in AML. Furthermore, we analysed minimal residual disease (MRD) in eight patients in complete remission. CD66 expression was associated with an abnormal B-cell differentiation pattern and with increases in CD34/CD19+ cells in all but one case. These findings suggest that an aberrant expression of CD66 could be used to investigate MRD in ALL. The association between CD66 reactivity and bcr-abl in adult ALL remains to be investigated. Received: 31 May 1999 / Accepted: 10 November 1999     

CD4+CD25+T细胞与支气管哮喘

本文就CD4^＋CD25^＋T细胞的调节机制，CD4^＋CD25^＋T细胞与变态反应的关系，以及CD4^＋CD25^＋T细胞在支气管哮喘发病机制中的作用作一综述。     

In Vitro Generation of Functional Dendritic Cells from Human Umbilical Cord Blood CD34<Superscript>+</Superscript> Cells by a 2-Step Culture Method

Dendritic cells (DCs) are the most potent antigen-presenting cells in terms of initiating primary T-cell-dependent immune responses. We devised a 2-step culture method for obtaining sufficient numbers of functional DCs from umbilical cord blood (CB) CD34+ cells. In the first step, CB CD34+ cells were expanded by stimulation with early-acting cytokines such as stem cell factor (SCF), flt3 ligand (FL), and thrombopoietin (TPO) to amplify the hematopoietic progenitor cells. In the second step, granulocyte-macrophage colony-stimulating factor and interleukin 4 were added, and incubation was continued for another 5 days to induce differentiation of the expanded cells into DCs. During the first step of culturing with TPO, SCF, and FL, the total numbers of nucleated cells gradually increased, peaking at 4 weeks (245.3-fold). During the second step, expression of CD1a, CD83, and CD86 increased. Electron microscopic findings showed that these cells had cytosolic expansion to form dendrites and major histocompatibility complex class II compartments, which are characteristic of DCs. Functional analyses revealed that these cells had phagocytic activity and were capable of stimulating allogeneic T-cells in vitro.     

Pleural tuberculosis in Harare, Zimbabwe: the relationship between human immunodeficiency virus, CD4 lymphocyte count, granuloma formation and disseminated disease

objective   To elucidate the relationship between HIV, CD4¹ count and pleural TB. method   In a prospective study, 94 patients presenting at two large Harare hospitals with clinically suspected pleural TB were enrolled over a 10-month period. All underwent standardized evaluation, closed pleural aspiration and biopsy. Patients receiving directly observed anti-TB therapy were followed-up. results   Pleural TB was diagnosed in 90 individuals (median age 33 years; range 18-65; 64 males); the seroprevalence of HIV was 85%. HIV-positive patients were older than HIV-negative individuals (median age 33 vs 23 years, P = 0.013) and had a significantly lower median CD4¹ count (191 vs 1106 × 10⁶/l respectively, P = 0.004). A CD4¹ count of <200 × 10⁶/l was associated with a length of illness >30 days (65% vs 37%; P = 0.05), a positive pleural fluid smear (37% vs 0%; P = 0.0006) and a positive pleural biopsy Ziehl-Neelsen stain (35% vs 7%; P = 0.021). However, a relationship between CD4¹ count and either pleural granuloma formation or radiological evidence of disseminated disease was not observed. conclusion   In sub-Saharan Africa, TB pleural effusions have become associated with older age, a chronic onset, and an increased mycobacterial load. These data emphasize the complex relationship between pleural TB, HIV infection and a low CD4¹ count.     

High cyclin-dependent kinase inhibitors in Bcl-2 and Bcl-xL-expressing CD34+-proliferating haematopoietic progenitors

We have previously described the isolation of primitive, slow-proliferating progenitors from normal, circulating CD34+ cells by using the fluorescent dye 5-6-carboxyfluorescein diacetate succinimidyl ester (CFDA-SE). CFDA-SE(bright) (primitive) and CFDA-SE(dim) (differentiating) cells were isolated following cytokine stimulation on the basis of their different proliferation rates. In the present work we analysed the expression levels of a number of proteins involved with differentiation, proliferation and survival/apoptosis in CFDA-SE(bright)/CD34+/slow-proliferating cells that were previously defined as progenitors capable of differentiating into different lineages. The aim of this work was to gain a better understanding of our model system in order to define some of the important parameters that regulate differentiation in haematopoietic progenitors. GATA-1 and PU.1 RNA levels were similar in freshly isolated (d 0) CD34+ and in CFDA-SE(bright) (bright) cells, whereas they increased in CFDA-SE(dim) (dim) cells. Accordingly, Nm23 was expressed at higher levels in bright cells. Moreover, bright cells had higher p21WAF1/CIP1, p27KIP1 and p16Ink4 protein levels than dim cells. Consistently, Cdc2 and Cdk2 kinase activity was much higher in the dim than in the slower proliferating bright cells. C-myc and p53 levels were higher in bright cells than in d 0 CD34+ and dim cells, and so was Bcl-xL, which followed the trend we have previously described for Bcl-2. Thus, bright cells, despite having a higher proliferation rate than the starting d 0 CD34+ population, have strikingly elevated levels of cyclin-dependent kinase inhibitors, which are likely to also act as inhibitors of differentiation.     

系统性红斑狼疮患者CD5+B细胞的测定和意义

目的探讨外周血中CD5 B细胞在系统性红斑狼疮(SLE)活动中的作用及相关性。方法利用流式细胞分析法对57例SLE患者和35名正常人群外周血CD5~ B细胞进行检测,并且同时检测抗dsDNA抗体、抗核抗体(ANA)、抗心磷脂抗体(ACL)、补体C3、C4。结果SLE患者CD5~ B细胞水平[(2．1 0．4)%]与正常人[(1．5±0．4)％]比较差异有统计学意义(P＜0．05),活动期SLE患者CD5~ B细胞水平(2．5±0．5)％显著高于稳定期(1．4±0．5)％；CD5 B细胞与dsDNA、ANA、抗心磷脂抗体(ACL)升高呈正相关,与补体c3呈负相关。结论系统性红斑狼疮患者外周血CD5~ B细胞明显升高,与SLE疾病活动有一定关系。     

IL-27 impact on NK cells activity: Implication for a robust anti-tumor response in chronic lymphocytic leukemia

Interleukin 27 (IL-27) belongs to IL-12 cytokine family, has shown anti-tumor potential in several solid tumors, as well as hematologic malignancies. IL-27 can inhibit tumor growth and progression through direct and indirect mechanisms, such as inhibition of proliferation, angiogenesis, induction of apoptosis in tumor cells, and anti-tumor immune response. B-CLL is characterized by remarkable immune perturbation, which leads to disease complications and reduced effectiveness of the treatment. Natural killer cells (NK) are considered as an important arm for the elimination of transformed cells. However, NK cells have shown significant impairment in patients with CLL. Here we analyzed the activity of recombinant human (rh) IL-27-stimulated NK cells in bone marrow (BM) and peripheral blood (PB) of CLL patients using cell surface flow cytometry assessment, and cytotoxicity assay. We showed that rhIL-27 can increase CD69 on NK cells both in BM and PB. Interestingly, BM-NK cells treated with rhIL-27 exhibited a significant increase in degranulation and NK cell-mediated cytotoxicity as compared with untreated NK cells, whereas it did not improve NK cell activity of PB. These observations added further explanation to the anti-tumor activity of IL-27 and also could pave the way to adoption immunostimulatory adjuvant for therapies in CLL.     

IL-27 and autoimmune rheumatologic diseases: The good,the bad,and the ugly

The footprint of cytokines is evident in almost every biological process, such as development, as well as the pathogenesis of the different diseases, immune responses to pathogens, etc. These small proteins are categorized into different functional classes; for instance, they can play a pro-inflammatory or anti-inflammatory role in different situations, or they can confer a polarization to the immune system. Interleukin (IL)-27 is a member of the IL-12 family. Antigen-presenting cells are the primary source of IL-27 production, which exerts its effects by bindings to the IL-27 receptor expressed on the surface of target cells. Interaction of IL-27 and IL-27 receptor leads to activation of the JAK-STAT and p38 MAPK signaling pathways. Most studies focused on the inflammatory effects of this cytokine, but gradually anti-inflammatory effects were also revealed for this cytokine, which changed the traditional perception of the function of this cytokine. The functionality of IL-27 in the pathogenesis of rheumatic diseases has been attributed to a double-blade sword. Hence, novel therapeutic approaches have been devised targeting IL-12 family that has been accompanied with promising results. In this review, we focused on the inflammatory and anti-inflammatory properties of IL-27 in different autoimmune rheumatologic diseases and its plausible therapeutic potentials.