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Circulating Lymphocytes (circulating + lymphocyte)
Selected AbstractsChronic Alcohol Consumption Is Associated With an Increased Cytotoxic Profile of Circulating Lymphocytes That May Be Related With the Development of Liver InjuryALCOHOLISM, Issue 5 2010Francisco Javier Laso Background:, Apoptosis has recently emerged as a key component of acute and chronic liver diseases and it could be related to alcoholic liver disease. In the present study, we attempted to analyze the cytotoxic profile of circulating lymphocytes in chronic alcoholic patients grouped according to ethanol intake status and presence of liver disease. Methods:, We investigate the phenotypic and functional behavior of different compartments of peripheral blood (PB) cytotoxic T and natural killer (NK) cells in chronic alcoholic patients without liver disease and active ethanol intake (AWLD group; n = 22), and in subjects with alcohol liver cirrhosis (ALC group; n = 22). Results:, AWLD patients showed an expansion of both CD4+/CD8+ cytotoxic T cells and NK/T cells, in association with an enhanced cytolytic activity against K562 cells and a higher ability to induce in vitro expression of the pro-apoptotic protein APO2.7 in HepG2 cells. Conversely, ethanol intake in ALC patients was associated with decreased NK cell numbers, a reduced cytotoxic activity against K562 cells without significant changes in the expression of APO2.7, and a pro-fibrotic profile of cytokine secretion. Conclusions:, Overall, our results suggest that alcoholic patients display different phenotypical and functional changes in circulating PB cytotoxic lymphocytes according to the presence of alcoholic liver disease, which could be related to the development and progress of liver injury. [source] Thermal Facilitation of Lymphocyte Trafficking Involves Temporal Induction of Intravascular ICAM-1MICROCIRCULATION, Issue 2 2009QING CHEN ABSTRACT Objective: Fever is associated with improved survival, although its beneficial mechanisms are poorly understood. Previous studies indicate that the thermal element of fever augments lymphocyte migration across high endothelial venules (HEVs) of lymphoid organs by increasing the intravascular display of a gatekeeper trafficking molecule, intercellular adhesion molecule-1 (ICAM-1). Here, we evaluated the spatio-temporal relationship between the thermal induction of intravascular ICAM-1 and lymphocyte trafficking. Methods: Intravascular ICAM-1 density was quantified by immunofluorescence staining in mice exposed to fever-range whole-body hyperthermia (39.5±0.5°C). ICAM-1,dependent lymphocyte trafficking was measured in short-term homing assays. Results: A linear relationship was observed between the duration of heat treatment and intravascular ICAM-1 density in HEVs with maximal responses requiring sustained (i.e., five hours) thermal stress. Circulating lymphocytes were found to sense incremental changes in ICAM-1 on HEVs, such that trafficking is proportional to the intravascular density of ICAM-1. We further identified a hydroxamate-sensitive shedding mechanism that restores ICAM-1 expression to homeostatic levels following the cessation of thermal stress. Conclusions: The time-dependent response to thermal stress indicates that ICAM-1 density governs the efficiency of lymphocyte interactions with HEVs in vivo. These studies highlight the dynamic role of the microcirculation in promoting immune surveillance during febrile inflammatory responses. [source] Clonally rearranged T-cell receptor , chain genes in HTLV-I carriers with abnormal, non-flower-like, lymphocytesEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2005Maria M. Sales Abstract:,Background:,The diagnosis of Adult T-cell leukemia/lymphoma ATLL subtypes in human T-lymphotropic virus type I (HTLV-I) carriers based in morphology and immunophenotype of lymphocytes can be challenger. We propose that polymerase chain reaction (PCR) amplification of the rearranged TCR gene in HTLV-I healthy carriers would be a convenient method for establishing the nature of the circulating T lymphocytes in asymptomatic HTLV-I carriers, presenting only mild and inconclusive signals of deviation from normality. Methods:,Using PCR, we analyzed the genetic recombination pattern of the T-cell , -chain receptor gene (TCR - ,) in order to identify clonal expansion of peripheral blood T lymphocytes in 17 HTLV-I-positive healthy carriers and in nine normal HTLV-I-negative blood donors. To evaluate the performance of PCR in detection of clonality, we also analyzed 18 patients with post-thymic/mature T-cell malignancies presenting circulating abnormal lymphocytes. Results:,Seven of the 17 HTLV-I positive individuals presented circulating abnormal lymphocytes; monoclonal or oligoclonal expansion of T-cells was detected in five of the 17 HTLV-I-positive individuals, all of them presenting abnormal lymphocytes. Clonal expansion was not detected in any of the negative controls or in any of the 12 remaining healthy carriers. All patients in the positive control group tested positive by PCR and Southern blots. Southern blots were negative for all 17 healthy carriers. Conclusions:,PCR amplification of segments of rearranged TCR- , is reliable for allowing early detection of small populations of clonal T cells in blood samples from asymptomatic HTLV-I carriers, providing an additional alert in the follow-up of carriers with abnormal circulating lymphocytes. [source] CD161 is a marker of all human IL-17-producing T-cell subsets and is induced by RORCEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2010Laura Maggi Abstract We have previously shown that human Th17 lymphocytes are characterized by the selective expression of IL-23 receptor (IL-23R), CCR6, CD161, and the transcription factor retinoic acid-related orphan receptor C (RORC), and originate from a CD161+CD4+ naïve T-cell precursor in response to the combined activity of IL-1, and IL-23. We show here that not only CD4+TCR,,+, but also CD8+TCR,,+, CD4,CD8, TCR,,+, and CD4,CD8, TCR,,+ circulating lymphocytes that produce IL-17 express the distinctive marker CD161 on their surface. In addition, we demonstrate that CD161 expression identifies CD8+ and CD4,CD8, umbilical cord blood T cells that already express RORC and IL-23R mRNA and that can be induced to differentiate into IL-17-producing cells in the presence of IL-1, and IL-23. Finally, we provide evidence that umbilical cord blood naïve CD4+CD161, T cells, upon lentivirus-mediated transduction with RORC2 can acquire the ability to express IL-23R, IL-1RI, and CD161, as well as to produce IL-17. Taken together, these data allow to conclude that T-cell subsets able to produce IL-17, as well as precursors of IL-17-producing T cells, exhibit surface expression of CD161, and that this feature is at least in part RORC2-dependent. [source] Evidence for the involvement of bacterial superantigens in psoriasis, atopic dermatitis, and Kawasaki syndromeFEMS MICROBIOLOGY LETTERS, Issue 1 2000Jeremy M. Yarwood Abstract A growing body of evidence implicates streptococcal and staphylococcal superantigens in the development of psoriasis, atopic dermatitis and Kawasaki syndrome. In each of these illnesses, an abnormal state of immunologic activity is observed. Superantigens, which have a unique ability to activate large numbers of lymphocytes, are likely to contribute to these disorders in a number of ways. The demonstrated activities of bacterial superantigens include increasing the number of circulating lymphocytes, with activation of autoreactive subsets, upregulation of tissue homing receptors on circulating lymphocytes, and local activation of immune cells within affected tissues. Through these and other mechanisms, superantigens have a proven ability to induce high levels of inflammatory cytokines and/or initiate autoimmune responses that contribute to the development of skin and vascular disorders. Though development of the illnesses discussed in this review are highly complex processes, superantigens may well play a critical role in their onset or maintenance. Understanding superantigen function may elucidate potential therapeutic strategies for these disorders. [source] Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines,HEPATOLOGY, Issue 4 2008Arnhild Schrage Transmigration through the liver endothelium is a prerequisite for the homeostatic balance of intrahepatic T cells and a key regulator of inflammatory processes within the liver. Extravasation into the liver parenchyma is regulated by the distinct expression patterns of adhesion molecules and chemokines and their receptors on the lymphocyte and endothelial cell surface. In the present study, we investigated whether liver sinusoidal endothelial cells (LSEC) inhibit or support the chemokine-driven transmigration and differentially influence the transmigration of pro-inflammatory or anti-inflammatory CD4+ T cells, indicating a mechanism of hepatic immunoregulation. Finally, the results shed light on the molecular mechanisms by which LSEC modulate chemokine-dependent transmigration. LSEC significantly enhanced the chemotactic effect of CXC-motif chemokine ligand 12 (CXCL12) and CXCL9, but not of CXCL16 or CCL20, on naive and memory CD4+ T cells of a T helper 1, T helper 2, or interleukin-10,producing phenotype. In contrast, brain and lymphatic endothelioma cells and ex vivo isolated lung endothelia inhibited chemokine-driven transmigration. As for the molecular mechanisms, chemokine-induced activation of LSEC was excluded by blockage of Gi -protein,coupled signaling and the use of knockout mice. After preincubation of CXCL12 to the basal side, LSEC took up CXCL12 and enhanced transmigration as efficiently as in the presence of the soluble chemokine. Blockage of transcytosis in LSEC significantly inhibited this effect, and this suggested that chemokines taken up from the basolateral side and presented on the luminal side of endothelial cells trigger T cell transmigration. Conclusion: Our findings demonstrate a unique capacity of LSEC to present chemokines to circulating lymphocytes and highlight the importance of endothelial cells for the in vivo effects of chemokines. Chemokine presentation by LSEC could provide a future therapeutic target for inhibiting lymphocyte immigration and suppressing hepatic inflammation. (HEPATOLOGY 2008.) [source] Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infectionHEPATOLOGY, Issue 6 2003Kazushi Sugimoto Hepatitis C virus (HCV) has a high propensity for persistence. To better define the immunologic determinants of HCV clearance and persistence, we examined the circulating HCV-specific T-cell frequency, repertoire, and cytokine phenotype ex vivo in 24 HCV seropositive subjects (12 chronic, 12 recovered), using 361 overlapping peptides in 36 antigenic pools that span the entire HCV core, NS3-NS5. Consistent with T-cell-mediated control of HCV, the overall HCV-specific type-1 T-cell response was significantly greater in average frequency (0.24% vs. 0.04% circulating lymphocytes, P = .001) and scope (14/36 vs. 4/36 pools, P = .002) among the recovered than the chronic subjects, and the T-cell response correlated inversely with HCV titer among the chronic subjects (R = ,0.51, P = .049). Although highly antigenic regions were identified throughout the HCV genome, there was no apparent difference in the overall HCV-specific T-cell repertoire or type-1/type-2 cytokine profile relative to outcome. Notably, HCV persistence was associated with a reversible CD4-mediated suppression of HCV-specific CD8 T cells and with higher frequency of CD4+CD25+ regulatory T cells (7.3% chronic vs. 2.5% recovered, P = .002) that could directly suppress HCV-specific type-1 CD8 T cells ex vivo. In conclusion, we found that HCV persistence is associated with a global quantitative and functional suppression of HCV-specific T cells but not differential antigenic hierarchy or cytokine phenotype relative to HCV clearance. The high frequency of CD4+CD25+ regulatory T cells and their suppression of HCV-specific CD8 T cells ex vivo suggests a novel role for regulatory T cells in HCV persistence. [source] Hematopoietic and immune recovery after allogeneic peripheral blood stem cell transplantation and bone marrow transplantation in a pediatric populationPEDIATRIC TRANSPLANTATION, Issue 4 2002Yoshihisa Nagatoshi Abstract: To compare the hematopoietic and immune recoveries after allogeneic transplantation with different cell sources, we analyzed the recovery patterns of blood components after allogeneic peripheral blood stem cell transplantation (PBSCT) in comparison with that after allogeneic bone marrow transplantation (BMT) in a pediatric population. Sixteen patients received PBSCT, and 24 received BMT between January, 1995 and March, 2000. The patients had acute lymphoblastic leukemia (ALL; n = 22), acute myelogenous leukemia (AML; n = 8), myelodysplastic syndrome (MDS; n = 3), or other diseases (n = 7). The median ages of patients in the PBSCT and BMT groups were 9 yr and 6 yr, respectively. Cyclosporin A (CsA) plus methotrexate or methylprednisolone was used as a graft-vs.-host disease (GvHD) prophylaxis regimen in the PBSCT group, whereas CsA alone or methotrexate alone was used in the BMT group. Circulating lymphocyte numbers and subpopulations determined by flow cytometric analysis were used as markers of immune recovery. In the PBSCT group, the median number of harvested CD34+ cells was 7.25 (range: 1.3,27.6) × 106/kg of the recipient's body weight, while the median number of harvested nucleated cells was 4.7 (range: 3.7,10.5) × 108/kg. All of the patients were engrafted. Myeloid engraftment occurred sooner after PBSCT than after BMT (median number of days to achieve absolute neutrophil counts (ANC) > 0.5 × 109/L; 11 and 15, respectively; p < 0.0001) and similar results were found for platelet engraftment (median number of days to achieve a platelet count of > 20 × 109/L; 12 and 21, respectively; p = 0.004). On the other hand, after PBSCT the absolute numbers of total circulating lymphocytes and lymphocyte subpopulations were not significantly different from those after BMT. The incidence of acute GvHD after PBSCT was the same as that after BMT, while chronic GvHD developed more frequently after PBSCT than after BMT (p = 0.005). In a pediatric population, the indications for PBSCT and BMT should be based on these findings in addition to regard for the donor's safety. [source] | ||||||||||