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Lymphocyte Activation (lymphocyte + activation)
Selected AbstractsClose association of CD8+/CD38bright with HIV-1 replication and complex relationship with CD4+ T-cell count,CYTOMETRY, Issue 4 2009Edouard Tuaillon Abstract Background: Measuring lymphocyte activation provides information in addition to CD4+ T-cell count for immune monitoring of HIV-1 infected patients. CD38 is a well-established activation marker that is generally analyzed on the whole population of CD8+ T-cells. Focusing specifically on CD38 high expression (CD8+/CD38bright) may be an interesting surrogate gating strategy because CD38bright characterizes principally activated memory cells. Methods: CD8+/CD38bright was investigated in 1,353 HIV-1 infected patients over a one-year period to establish relevant cutoff values and clarify the relationships of this marker with HIV-1 RNA viral load (VL) and CD4+ T-cell count. Results: The CD8+/CD38bright (>8,500 CD38 binding site per cells) is well correlated with HIV-1 VL (r = 0.87, P < 0.001) in this longitudinal follow-up of nonimmunodepressed patients that initiated antiviral therapy (ART). In aviremic patients on ART, the marker was highly predictive of VL rebound (sensitivity 93%, specificity 64% for a VL level of detection >200 copies/ml). While the CD8+/CD38bright moderately correlated with CD4+ T-cell count independently of the VL (r = ,0.37, P < 0.001), it increased dramatically in aviremic patient groups that exhibited profound CD4+ T-cell depletion (median 39% for CD4+ T-cell counts <50/mm3). This result indicates that other additional immunological and/or viral factors than readily detectable HIV-1 replication appears to be involved in T-cell activation of immunodepressed individuals. Conclusions: CD8+/CD38bright is an effective marker for monitoring T-cell activation, which is a central factor of HIV-1 pathogenesis. This gating strategy requires only a single additional staining in conventional four color CD4 protocols. © 2008 Clinical Cytometry Society [source] ESCI award lecture: from a little mouse to rationale medicine for bone lossEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2009A. Leibbrandt Abstract Completion of the human genome is one of the many significant milestones in the new era of systems biology. The current phase of genomic studies is focused upon parsing this new found genetic data with respect to scientific interest, and economic and health impact applications. As the sequences are now available and whole genome single nucleotide polymorphism maps for multiple human diseases will be available with the advent of modern genomics, the big challenge is to determine the function of these genes in the context of the entire organism. The emphasis is therefore on functional genomic analysis that represents the new front-line and limiting factor for realizing potential benefits of genome-based science. Defined gene targeting has been proven to be particularly useful as loss of expression mutants can reveal essential functions of molecules and the pathogenesis of disease. Using gene-targeted mice, my group has over the years identified genes that control heart and lung functions [1,5]; apoptosis [6,9]; lymphocyte activation [10,14]; cancer [15,17]; pain [18]; diabetes [19]; fertility [20] or wound healing [21]. In this study, I would like to review our work on RANKL in more detail. [source] Identification of pro-interleukin 16 as a novel target of MAP kinases in activated T lymphocytesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2004Arian Laurence Abstract T lymphocyte activation is controlled by a coordinated web of tyrosine and serine kinases. There is a large body of information about tyrosine kinase substrates in T cells but analysis of serine kinase substrates has been more difficult. Recently we described an antiserum that recognizes serine-phosphorylated peptides corresponding to the substrate sequences for AGC serine kinases. This antiserum, termed PAP-1 (phospho antibody for proteomics-1), has proven useful for probing the serine phosphoproteome of antigen receptor-activated T lymphocytes. The present study shows that PAP-1 can also be used to explore serine kinases activated by cytokines and chemokines in T cells. Using PAP-1, together with proteomic analysis, the precursor form of the cytokine IL-16 (ProIL-16) was shown to be phosphorylated on Ser144 in antigen receptor-, SDF1,- and IL-2-activated T cells. Genetic and pharmacological-inhibitor experiments showed that the phosphorylation of ProIL-16 is dependent on activation of the kinases Erk1/2. IL-16 is secreted by mitogen-activated T cells, and the biochemical link between ProIL-16 and Erk1/2, revealed by studies with PAP-1, prompted analysis of the role of MAP kinases in this response. We show that TCR-mediated secretion of IL-16 is dependent on MAP kinases. The present study thus reveals how phosphoproteomic analysis opens previously unrecognized avenues for research, and yields novel insights about targets for MAP kinases in T lymphocytes. [source] T-cell interleukin-6 receptor binding in interferon-,-1b-treated multiple sclerosis patientsEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2000P. Bongioanni Multiple sclerosis (MS) is a T-cell-mediated autoimmune demyelinating disease of the central nervous system, associated with an altered cytokine network. We previously assayed peripheral blood T-lymphocyte binding for two prototypic cytokines, tumour necrosis factor-, (TNF-,) and interleukin-6 (IL-6), and found that T cells from MS patients had significantly more TNF-, and IL-6 receptors than those from healthy controls. In the present work, paralleling a previous one on T-cell TNF-, binding, we studied the effect of interferon (IFN)-,-1b treatment on T-lymphocyte IL-6 binding in patients with relapsing,remitting MS. T cells from MS patients had significantly (P < 0.001) higher amounts of IL-6 receptors than those from controls [292 ± 6 vs. 228 ± 8 (mean ± SEM) receptors per cell, respectively], whereas the ligand-receptor affinity values were similar in the two groups [26.2 ± 0.7 and 25.7 ± 0.4 (mean ± SEM) pmoles/l, respectively]. After a 3-month IFN-,-1b treatment, they showed a significant decrease in IL-6 binding [266 ± 7 (mean ± SEM) receptors per cell]. After 6 and 9 months, T-cell IL-6 Bmax values were even lower [258 ± 8 and 251 ± 8 (mean ± SEM) receptors per cell]. Since an increased IL-6 binding might be linked to a lymphocyte activation, our data give further support for an enhanced immune response in patients with MS. Our data seem to demonstrate that the major effects of IFN-,-1b treatment result in a decrease of T-cell activation. [source] CARMA1-mediated NF-,B and JNK activation in lymphocytesIMMUNOLOGICAL REVIEWS, Issue 1 2009Marzenna Blonska Summary:, Activation of transcription factor nuclear factor-,B (NF-,B) and Jun N-terminal kinase (JNK) play the pivotal roles in regulation of lymphocyte activation and proliferation. Deregulation of these signaling pathways leads to inappropriate immune response and contributes to the development of leukemia/lymphoma. The scaffold protein CARMA1 [caspase-recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1] has a central role in regulation of NF-,B and the JNK2/c-Jun complex in both B and T lymphocytes. During last several years, tremendous work has been done to reveal the mechanism by which CARMA1 and its signaling partners, B cell CLL-lymphoma 10 and mucosa-associated lymphoid tissue 1, are activated and mediate NF-,B and JNK activation. In this review, we summarize our findings in revealing the roles of CARMA1 in the NF-,B and JNK signaling pathways in the context of recent advances in this field. [source] A T2 cytokine environment may not limit T1 responses in human immunodeficiency virus patients with a favourable response to antiretroviral therapyIMMUNOLOGY, Issue 1 2006Patricia Price Summary Low-level production of interferon-, (IFN-,) marks human immunodeficiency virus (HIV)-induced immunodeficiency and has been ascribed to a bias towards T2 cytokines. This was investigated in two cross-sectional studies of HIV patients who were immunodeficient when they began antiretroviral therapy (ART) and had stable increases in CD4 T-cell counts. Blood leucocytes were assessed unstimulated or after stimulation with cytomegalovirus (CMV), anti-CD3 or mitogen. IFN-, and interleukin (IL)-5 responses were initially assessed by enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) and enzyme-linked immunosorbent assay (ELISA). We then adopted a sensitive reverse transcription,polymerase chain reaction (RT,PCR) system to assess IFN-,, IL-5, IL-4 and IL-4,2 (an inhibitory splice variant of IL-4) mRNA. The results were correlated with putative serological markers of a T1 [lymphocyte activation gene-3 (LAG-3), CD26] or a T2 [CD30, immunoglobulin E (IgE)] cytokine environment. IL-5 production and IgE levels were elevated in patients. IgE levels did not correlate with IFN-,, but showed an inverse correlation with IL-5 released in culture (P = 0·05). The levels of IL-4, IFN-,, IL-5 and IL-4,2 mRNA were correlated after anti-CD3 stimulation, where IL-5 was the best predictor of IFN-, mRNA (P = 0·006). Weak positive correlations were evident between CD30 and cytokine mRNA levels, whilst IgE correlated inversely with IL-4, IL-4,2, IL-5 and IFN-, mRNA levels. These analyses provide no evidence for an inverse relationship between T1 and T2 cytokine responses in HIV patients, but suggest that the elevation of IgE marks low cytokine responses. [source] Cloning of rat lymphocyte activation gene-3 (Lag3; CD223) cDNA and its mRNA expression in rat tissues,INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2004T. Chun Summary Rat lymphocyte activation gene-3 (Lag3; CD223) cDNA contains an open reading frame (1575 bp) encoding 525 amino acids. Rat Lag3 mRNA transcript was detected as a single species of approximately 2 kb from phytohemagglutinin (PHA)-stimulated lymphocytes. Further analysis revealed that rat Lag3 mRNA was mainly expressed in lymphoid tissues. [source] Mechanistic study of saikosaponin-d (Ssd) on suppression of murine T lymphocyte activationJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2009Vincent Kam Wai Wong Abstract Saikosaponin-d (Ssd) is a triterpene saponin derived from the medicinal plant, Bupleurum falcatum L. (Umbelliferae). Previous findings showed that Ssd exhibits a variety of pharmacological and immunomodulatory activities including anti-inflammatory, anti-bacterial, anti-viral and anti-cancer effects. In the current study we have investigated the effects of Ssd on activated mouse T lymphocytes through the NF-,B, NF-AT and AP-1 signaling pathways, cytokine secretion, and IL-2 receptor expression. The results demonstrated that Ssd not only suppressed OKT3/CD28-costimulated human T cell proliferation, it also inhibited PMA, PMA/Ionomycin and Con A-induced mouse T cell activation in vitro. The inhibitory effect of Ssd on PMA-induced T cell activation was associated with down-regulation of NF-,B signaling through suppression of IKK and Akt activities. In addition, Ssd suppressed both DNA binding activity and the nuclear translocation of NF-AT and activator protein 1 (AP-1) of the PMA/Ionomycin-stimulated T cells. The cell surface markers like IL-2 receptor (CD25) were also down-regulated together with decreased production of pro-inflammatory cytokines of IL-6, TNF-, and IFN-,. These results indicate that the NF-,B, NF-AT and AP-1 (c-Fos) signaling pathways are involved in the T cell inhibition evoked by Ssd, so it can be a potential candidate for further study in treating T cell-mediated autoimmune conditions. J. Cell. Biochem. 107: 303,315, 2009. © 2009 Wiley-Liss, Inc. [source] A possible CD1a Langerhans cell,mast cell interaction in chronic hyperplastic candidosisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 6 2007Ahmed Ali Aims:, T lymphocyte,antigen-presenting cell (APC) interaction plays a central role in T lymphocyte activation and APC maturation. We therefore studied the CD1a-positive Langerhans cells with respect to receptor activator of nuclear factor kappa B ligand (RANKL)-positive cells in chronic hyperplastic candidosis (CHC). Materials and methods:, Tissue sections of CHC were compared with leukoplakia and healthy oral mucosa using RANKL and CD1a monoclonal antibodies in an avidin,biotin peroxidase complex protocol. Two different antigen-retrieval protocols, pepsin preincubation and Tris,EDTA heat treatment, were used. Results:, CD1a-positive Langerhans cells were in healthy and leukoplakia epithelium found in the middle layer, but in CHC in all layers of the epithelium, at the basement membrane and as mononuclear round cells in the lamina propria. Use of pepsin digestion enabled studies of mast cells and their activation in the form of degranulation of RANKL. Conclusions:, The numerical, morphological and topographical versatility of the CD1a-positive Langerhans cells in CHC can be clarified by dendritic cell (DC) recruitment into the epithelium. RANK-positive and RANKL-sensitive DCs have ample opportunity to interact with local T lymphocytes. Use of an optimized antigen-retrieval protocol enabled demonstration of an active engagement (degranulation) of mast cells, which represent a rapidly available source of soluble RANKL. [source] Effects of Naturally Occurring Stilbene Glucosides from Medicinal Plants and Wine, on Tumour Growth and Lung Metastasis in Lewis Lung Carcinoma-Bearing MiceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2000YOSHIYUKI KIMURA Stilbene glucosides are naturally occurring phytoalexins, found in a variety of medicinal plants. Among the stilbene derivatives, resveratrol 3- O -D-glucoside (piceid) is found in grapes and wine. We studied the effects of stilbene glucosides isolated from medicinal plants and grapes on tumour growth and lung metastasis in mice bearing highly metastastic Lewis lung carcinoma (LLC) tumours. We also studied the inhibitory effects of stilbene glucosides on differentiation of human umbilical vein endothelial cells (HUVECs) to form a capillary network. Tumour growth in the right hind paw and lung metastasis were inhibited by oral administration of the stilbene glucosides, piceid and 2,3,5,4,-tetrahydroxystilbene-2- O -D-glucoside for 33 consecutive days, in LLC-bearing mice. As the number of CD8+ and NK1.1+ T cells in the spleen was not affected, the inhibitory effects of these stilbene glucosides on tumour growth and lung metastasis could not be explained by natural killer or cytotoxic T lymphocyte activation. Piceid inhibited the DNA synthesis in LLC cells at a concentration of 1000 ,m, but not at lower concentrations (10,100 ,M). 2,3,5,4,-Tetra-hydroxystilbene-2- O -D-glucoside also inhibited DNA synthesis in LLC cells (IC50 81 ,M). In addition, both stilbene glucosides inhibited the formation of capillary-like tube networks (angiogenesis) of HUVECs at concentrations of 100 to 1000 ,M. We suggest that the antitumour and antimetastatic activity of the stilbene glucosides, piceid and 2,3,5,4,-tetrahydroxystilbene-2- O -D-glucoside, might be due to the inhibition of DNA synthesis in LLC cells and angiogenesis of HUVECs. [source] Tetraspanins and Intercellular InteractionsMICROCIRCULATION, Issue 3 2001MARÍA YÁÑEZ-MÓ ABSTRACT The superfamily of tetraspanins comprises a group of polypeptides with four transmembrane domains that form large supramolecular structures in the plasma membrane through their associations to multiple integral membrane proteins. They are involved in homo- and heterotypic intercellular interactions in different processes such as hematopoiesis, lymphocyte activation, cancer metastasis, and fertilization. Intercellularly located tetraspanins regulate the juxtacrine activity of growth factors, cell fusion, and myelin formation. On the other hand, in motile cells they relocalize from cell-cell junctions to actin-based structures such as filopodia or growth cones and regulate cell motility in wound healing and angiogenesis processes. [source] Activation of human T lymphocytes under conditions similar to those that occur during exposure to microgravity: A proteomics studyPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 7 2005Angela Risso Abstract A number of experiments, conducted under microgravity conditions, i.e. in space shuttle biolaboratories or in ground based systems simulating the conditions occurring in microgravity, show that in hypogravity, in vitro human lymphocyte activation is severely impaired. However, very early stimulation steps of T lymphocytes are not compromised, since CD69 receptor, the earliest membrane activation marker, is expressed by T cells at a level comparable to that observed on 1 g activated lymphocytes. Since CD69 engagement, together with submitogenic doses of phorbol esters, transduces an activation signal to T lymphocytes, we undertook a comparative study on the stimulation mediated through this receptor on human CD3+ cells cultured under conditions similar to those which occur during exposure to microgravity, i.e. in clinorotation, or at 1 g. During the early hours of activation, increased levels of intracellular calcium and increased mitochondrial membrane potential were detectable in clinorotating as well as in 1 g cells. However, after 48 hours clinorotation, interleukin 2 production by T lymphocytes was significantly reduced and cell proliferation was greatly decreased. By means of a differential proteomics approach on T cells activated in clinorotation or at 1 g for 48 hours, we were able to detect statistically significant quantitative protein alterations. Seven proteins with modified expression values were identified; they are involved in nucleic acids processing, proteasome regulation and cytoskeleton structure. [source] Elevated NK Cell Cytotoxicity, CD158a Expression in NK Cells and Activated T Lymphocytes in Peripheral Blood of Women with IVF FailuresAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Viktor P. Chernyshov Citation Chernyshov VP, Sudoma IO, Dons'koi BV, Kostyuchyk AA, Masliy YV. Elevated NK cell cytotoxicity, CD158a expression in NK cells and activated T lymphocytes in peripheral blood of women with IVF failures. Am J Reprod Immunol 2010; 64: 58,67 Problem, The aim of this study was to evaluate the role of elevated natural killer cytotoxicity (NKc) in women with multiple implantation failures (IF) in vitro fertilization,embryo transfer (IVF,ET) cycles. Methods of study, Seventy-nine antiphospholipid antibodies-negative women with IF including 33 women with elevated NKc were selected for investigation. K-562 cell line was used to evaluate NKc. Lymphocyte subsets, intracellular cytokines [interferon (IFN)-,, interleukin (IL)-4, tumour necrosis factor, IL-10], expression of activating markers [CD69, human leukocyte antigen (HLA)-DR], CD8, KIR (CD158a), CD95, and chemokine receptors (CXCR3, CCR4) were estimated by flow cytometry. Results, In women with IF, levels of NKc were higher than in IVF successful women. IF was associated with higher expression of CD8, CD158a, and HLA-DR in NK cells, activating markers in T lymphocytes, and lower levels of CCR4+ and IL-4+ T lymphocyte subsets. Predictive value of single elevated NKc for IVF success was 0.85, but addition of two other abnormal parameters resulted in its decrease to <0.39. Conclusions, Elevated NKc is negative factor, though not critical for implantation in IVF cycles. Immune mechanism of IVF failure includes not only elevated NKc but also some other factors, such as elevated expression of CD8 and CD158a on NK cells, T lymphocyte activation, and diminished T helper 2 parameters. [source] Silencing S1P1 Receptors Regulates Collagen-V Reactive Lymphocyte-Mediated Immunobiology in the Transplanted LungAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2008M. Chiyo Type V collagen (col[V])-reactive lymphocytes contribute to lung transplant rejection, but the mechanisms for emigration into the graft are unknown. Sphingosine-1-phosphate-1 receptors (S1P1R) are believed to be required for lymphocyte emigration in other studies, but their role in col(V)-reactive lymphocyte rejection responses is not known. Utilizing small interfering RNA (siRNA) to reduce S1P1R expression on col(V)-reactive lymphocytes, we examined the role of S1P1R in the rejection response. Quantitative polymerase chain reaction (PCR) revealed strong expression of S1P1R messenger RNA (mRNA)on col(V)-reactive lymphocytes isolated from immunized rats. S1P1R -specific siRNA (S1P1R siRNA) reduced expression of S1P1R mRNA and protein, whereas scramble siRNA (SC siRNA) had no effect. Adoptive transfer of lymphocytes treated with S1P1R siRNA to rat Wistar Kyoto (WKY) lung isograft recipients resulted in retention of cells within the liver with fewer cells in mediastinal lymph nodes when compared to cells exposed to SC siRNA. S1P1R -deficient cells proliferated in response to alloantigens, but not in response to col(V), and produced less interferon (IFN)-, in response to col(V) compared to controls. Downregulating S1P1R did not affect production of interleukin (IL)-10and tumor necrosis factor (TNF)-,, or expression of adhesion molecules critical for migration, but prevented rejection pathology and lowered local levels of IFN-, post adoptive transfer. These data demonstrate novel roles of S1P1R, which include regulating emigration and modulating lymphocyte activation. [source] Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissuesARTHRITIS & RHEUMATISM, Issue 7 2010Mohammed F. Shamji Objective Prior reports document macrophage and lymphocyte infiltration with proinflammatory cytokine expression in pathologic intervertebral disc (IVD) tissues. Nevertheless, the role of the Th17 lymphocyte lineage in mediating disc disease remains uninvestigated. We undertook this study to evaluate the immunophenotype of pathologic IVD specimens, including interleukin-17 (IL-17) expression, from surgically obtained IVD tissue and from nondegenerated autopsy control tissue. Methods Surgical IVD tissues were procured from patients with degenerative disc disease (n = 25) or herniated IVDs (n = 12); nondegenerated autopsy control tissue was also obtained (n = 8) from the anulus fibrosus and nucleus pulposus regions. Immunohistochemistry was performed for cell surface antigens (CD68 for macrophages, CD4 for lymphocytes) and various cytokines, with differences in cellularity and target immunoreactivity scores analyzed between surgical tissue groups and between autopsy control tissue regions. Results Immunoreactivity for IL-4, IL-6, IL-12, and interferon-, (IFN,) was modest in surgical IVD tissue, although expression was higher in herniated IVD samples and virtually nonexistent in control samples. The Th17 lymphocyte product IL-17 was present in >70% of surgical tissue fields, and among control samples was detected rarely in anulus fibrosus regions and modestly in nucleus pulposus regions. Macrophages were prevalent in surgical tissues, particularly herniated IVD samples, and lymphocytes were expectedly scarce. Control tissue revealed lesser infiltration by macrophages and a near absence of lymphocytes. Conclusion Greater IFN, positivity, macrophage presence, and cellularity in herniated IVDs suggests a pattern of Th1 lymphocyte activation in this pathology. Remarkable pathologic IVD tissue expression of IL-17 is a novel finding that contrasts markedly with low levels of IL-17 in autopsy control tissue. These findings suggest involvement of Th17 lymphocytes in the pathomechanism of disc degeneration. [source] Inflammatory cytokine gene expression in the urinary sediment of patients with lupus nephritisARTHRITIS & RHEUMATISM, Issue 5 2003Rebecca Wing-Yan Chan Objective Lupus nephritis is characterized by intrarenal inflammation and lymphocyte activation. In the present study, the expression of cytokine genes in the urinary sediment of patients with systemic lupus erythematosus (SLE) was examined. Methods We studied 3 SLE patient groups (25 with active lupus nephritis [active group], 25 with inactive SLE and previous renal involvement [remission group], 20 with inactive SLE and no history of renal involvement [nonrenal SLE group]) and 2 control groups (10 patients with noninflammatory renal diseases [non-SLE group] and 10 healthy volunteers [healthy group]). Cytokine gene expression in the urinary sediment was studied by real-time quantitative polymerase chain reaction. Results Expression of interferon-, (IFN,) in urinary sediment was significantly higher in the active group than in all other groups (P < 0.001 by Kruskal-Wallis test). Among the SLE patient groups, there was a close correlation between IFN, expression and the overall SLE Disease Activity Index (SLEDAI) score (Spearman's r = 0.590, P < 0.001) and the SLEDAI renal score (r = 0.642, P < 0.001). Urinary expression of interleukin-2 (IL-2) in the active group was significantly higher than that in the healthy group (P = 0.046) but not in the remission or nonrenal SLE groups. There was no difference in the levels of IL-4 expression among the SLE groups. Conclusion We found a predominance of Th1 cytokine in the urinary sediment of patients with active lupus nephritis. Measurement of cytokine gene expression in urinary sediment may be a useful noninvasive tool for assessing the severity of renal involvement in SLE. [source] Overexpression of caspase recruitment domain (CARD) membrane-associated guanylate kinase 1 (CARMA1) and CARD9 in primary gastric B-cell lymphomaCANCER, Issue 9 2005Shigeo Nakamura M.D. Abstract BACKGROUND Although caspase recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) and CARD9 play important roles in lymphocyte activation, the significance of CARMA1 and CARD9 in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma remains to be elucidated. METHODS By using reverse transcription-polymerase chain reaction analysis, the expression levels of mRNA of CARMA1, CARD9, Bcl10, and the apoptosis inhibitor 2 (API2)-MALT1 chimeric transcript were determined in tissue specimens from 65 patients with primary gastric B-cell lymphoma (43 patients with low-grade MALT lymphoma, 16 patients with MALT lymphoma plus diffuse large B-cell lymphoma [DLBL], and 6 patients with DLBL without MALT lymphoma) and in tissue specimens from 18 patients with chronic gastritis. The expression levels of CARMA1 and BCL10 were examined immunohistochemically in 30 patients with lymphoma. RESULTS CARMA1 mRNA was detected in 55% of lymphoma patients but in only 17% of chronic gastritis patients. The positive rates for CARD9, Bcl10, and API2-MALT1 chimeric transcript in the lymphoma patients were 48%, 98%, and 8%, respectively, whereas the 3 molecules were not detected in any specimens from patients with chronic gastritis. The expression of CARMA1 and CARD9 was frequent in the Helicobacter pylori -negative patients (100% and 86%, respectively), in the API2-MALT1 chimeric transcript-positive patients (100% and 100%, respectively), and in the specimens from patients who did not respond to H. pylori eradication (76% and 71%, respectively). In addition, CARMA1 expression was positive more frequently in patients of DLBL without MALT lymphoma (100%) than in patients of MALT lymphoma (51%). CARMA1 protein expression was correlated significantly with the expression of CARMA1 mRNA and also with the expression of nuclear BCL10. CONCLUSIONS The overexpression of CARMA1 and CARD9 presumably is associated with the development or progression of gastric B-cell lymphoma, especially among patients who have disease in which the pathogenesis is not related to H. pylori. Cancer 2005. © 2005 American Cancer Society. [source] Selective effects of Lactobacillus casei Shirota on T cell activation, natural killer cell activity and cytokine productionCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2010H. Dong Summary Modulation of host immunity is an important potential mechanism by which probiotics confer health benefits. This study was designed to investigate the effects of a probiotic strain, Lactobacillus casei Shirota (LcS), on immune function using human peripheral blood mononuclear cells (PBMC) in vitro. In addition, the role of monocytes in LcS-induced immunity was also explored. LcS promoted natural killer (NK) cell activity and preferentially induced expression of CD69 and CD25 on CD8+ and CD56+ subsets in the absence of any other stimulus. LcS also induced production of interleukin (IL)-1,, IL-6, tumour necrosis factor (TNF)-,, IL-12 and IL-10 in the absence of lipopolysaccharide (LPS). In the presence of LPS, LcS enhanced IL-1, production but inhibited LPS-induced IL-10 and IL-6 production, and had no further effect on TNF-, and IL-12 production. Monocyte depletion reduced significantly the impact of LcS on lymphocyte activation, cytokine production and natural killer (NK) cell activity. In conclusion, LcS activated cytotoxic lymphocytes preferentially in both the innate and specific immune systems, which suggests that LcS could potentiate the destruction of infected cells in the body. LcS also induced both proinflammatory and anti-inflammatory cytokine production in the absence of LPS, but in some cases inhibited LPS-induced cytokine production. Monocytes play an important role in LcS-induced immunological responses. [source] Roles of CD147 on T lymphocytes activation and MMP-9 secretion in Systemic Lupus ErythematosusJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2007Gina Pistol Abstract The cellular and molecular mechanisms involved in many abnormalities described in Systemic Lupus Erythematosus (SLE) are still unclear. Some of these abnormalities referred to the hyperactivation of T lymphocytes and the enhanced secretion of MMP-9 by peripheral blood mononuclear cells (PBMCs). Therefore, in this paper we investigated the potential role of CD147 molecule in these abnormalities. Our results demonstrated that CD147 molecule is overexpressed on CD3+T lymphocytes from SLE patients when compared with CD3+T lymphocytes from healthy donors. Monoclonal anti-CD147 antibodies, MEM-M6/1 clone, were able to inhibit protein tyrosine phosphorylation only in CD3 × CD28 costimulated T lymphocytes from SLE patients. However, this monoclonal antibody was unable to inhibit the enhanced activity of MMP-9 secreted by SLE PBMCs. [source] Cytokine detection in HIV-1/HHV-8 co-infected subjectsCELL BIOCHEMISTRY AND FUNCTION, Issue 3 2002Agostino Pugliese Abstract In a previous work we have evaluated some immunologic and haematologic parameters of HIV-1 positive subjects co-infected with HHV-8. A worsening of these values were generally described in these patients as compared with those HIV-1 positive, but negative for HHV-8. Now we have studied the influence of HHV-8 co-infection of HIV-1 positive subjects on the production of some cytokines to make clear the question of its role in the immuno-deregulation of the above-mentioned subjects. In particular we have analysed serum levels of IL-4 and IL-10, Th2 type T cells cytokines, IFN-,, an indirect marker of Th1 cells activation and IL-18, a cytokine produced by monocytic-macrophagic cells, which is able to induce IFN-, production and Th1 T lymphocytes activation. No significant differences were found as regards the IFN-, serum levels (92.1,±,24.3 pg ml,1 in the case of HIV-1 positive/HHV-8 negative subjects and 96.0,±,17.4 pg ml,1 in those HIV-1 positive/HHV-8 positive). In healthy subjects the mean level of this cytokine was 17.6,±,5.2 pg ml,1 (significant difference with both the former values at p,<,0.001). Moreover IL-4 and IL-10, which were undetectable in healthy individuals, showed the following values in HIV-1positive/HHV-8 negative subjects: 31.9,±,2.7 pg ml,1 and 119.8,±,85.1 pg ml,1 respectively and in HIV-1 positive/HHV-8 positive subjects: 30.4,±,4.8 pg ml,1 and 69.4,±,65.3 pg ml,1 (not significant differences). In contrast IL-18 reached a mean level of 1001.2,±,360.5 pg ml,1 in HIV-1 positive/HHV-8 negative subjects, but showed a significant reduction in HIV-1 positive/HHV-8 positive subjects (737.6,±,284.3 pg ml,1,p,<,0.05) and presented very low levels in healthy individuals (21.3,±,30.3 pg ml,1). Moreover a significant correlation (,0.984,p,<,0.001) was noticed between IL-18 reduction in HIV-1 positive subjects co-infected with HHV-8 and the degree of positivity of HHV-8. These data suggest that HHV-8 co-infection has no influence on the switch Th1, Th2 in HIV-1 positive subjects, but is able to reduce IL-18 production, useful for Th1 subset restoration. Copyright © 2002 John Wiley & Sons, Ltd. [source] | |||||||||||||