Lymphocyte Phenotype (lymphocyte + phenotype)

Distribution by Scientific Domains


Selected Abstracts


Specific Alteration of Peripheral Cytotoxic Cell Perforin Expression in Alcoholic Patients: A Possible Role in Alcohol-Related Diseases

ALCOHOLISM, Issue 11 2003
Pascal Perney
Background: The association between chronic alcohol consumption and an increasing risk of infectious and neoplastic disease is related to an impairment of cellular immunity. However, studies of the number and activity of lymphocyte subsets show highly variable results. The aim of this study was to assess the expression of perforin, one of the main molecular agents of T and natural killer (NK) cell,mediated cytotoxicity, in alcoholic patients without cirrhosis. Methods: Eighteen patients with chronic alcoholism were prospectively included and compared with 18 age- and sex-matched healthy volunteers. Signs of hepatic insufficiency or portal hypertension, viral co-infection, other serious medical illness, and immune-related medications were exclusion criteria. Lymphocyte phenotype was assessed, and perforin expression was analyzed by flow cytometry in CD3+CD56+ T cells and NK cells. Granzyme synthesis was also evaluated in 11 of the 18 patients and compared with that of 11 age- and sex-matched controls. Results: The mean number of white blood cells and lymphocytes was not different between the controls and alcoholic patients, whereas the mean number of NK cells was significantly decreased in alcoholic patients (110 ± 79/mm3 versus 271 ± 192/mm3; p < 0.03). Perforin expression in T CD3+/CD56+ and in NK cells was significantly decreased in alcoholic patients compared with controls: 16 ± 3% vs. 36 ± 4% (p < 0.03) and 65 ± 15% vs. 78 ± 9% (p= 0.04), respectively. The percentage of cells expressing granzyme was similar in both groups. Conclusions: A decrease in perforin expression by cytotoxic cells could be a major factor in explaining the physiopathologic mechanisms of several alcohol-associated diseases. [source]


Unique Susceptibility of the Fetal Thymus to Feline Immunodeficiency Virus Infection: An Animal Model for HIV Infection In Utero1

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2001
CALVIN M. JOHNSON
PROBLEM: Human infants infected in utero with HIV develop thymus insufficiency and progress to AIDS sooner than infants infected peripartum. However, direct analysis of the thymus is difficult due to limited tissue access and variable timing of vertical transmission. METHOD OF STUDY: Fetal and neonatal cats were inoculated with feline immunodeficiency virus (FIV) at an equivalent infectious dose. The thymus, blood, and lymph nodes were harvested and compared at 23 and 46 days post-inoculation (p.i.) and also compared to sham-inoculated, age-matched controls. Lymphocyte phenotypes were analyzed by flow cytometry and virus burden was quantified in histologic sections and by virus isolation from plasma. RESULTS: Fetal cats inoculated with FIV had acute thymus atrophy at birth, which coincided with peak viremia. At 46 days p.i., thymus size and cell composition rebounded and supported increased productive infection. In contrast, neonatal cats inoculated with FIV developed chronic thymus atrophy and degeneration, which was associated with decreasing productive infection and low-level viremia. CONCLUSIONS: The fetal thymus is uniquely vulnerable to acute, transient depletion and high-level productive infection. The neonatal thymus is less vulnerable to acute changes, and responds through progressive atrophy and declining productive infection. Reduced immune competence, as reflected by the failure to control virus replication, may contribute to the accelerated progression of FIV and HIV infections in utero. [source]


A novel subpopulation of B-1 cells is enriched with autoreactivity in normal and lupus-prone mice

ARTHRITIS & RHEUMATISM, Issue 12 2009
Xuemei Zhong
Objective B-1 cells have long been suggested to play an important role in lupus. However, reports to date have been controversial regarding their pathogenic or protective roles in different animal models. We undertook this study to investigate a novel subpopulation of B-1 cells and its roles in murine lupus. Methods Lymphocyte phenotypes were assessed by flow cytometry. Autoantibody secretion was analyzed by enzyme-linked immunosorbent assay, autoantigen proteome array, and antinuclear antibody assay. Cell proliferation was measured by thymidine incorporation and 5,6-carboxyfluorescein succinimidyl ester dilution. B cell Ig isotype switching was measured by enzyme-linked immunospot assay. Results Anti,double-stranded DNA (anti-dsDNA) autoantibodies were preferentially secreted by a subpopulation of CD5+ B-1 cells that expressed programmed death ligand 2 (termed L2pB1 cells). A substantial proportion of hybridoma clones generated from L2pB1 cells reacted to dsDNA. Moreover, these clones were highly cross-reactive with other lupus-related autoantigens. L2pB1 cells were potent antigen-presenting cells and promoted Th17 cell differentiation in vitro. A dramatic increase of circulating L2pB1 cells in lupus-prone BXSB mice was correlated with elevated serum titers of anti-dsDNA antibodies. A significant number of L2pB1 cells preferentially switched to IgG1 and IgG2b when stimulated with interleukin-21. Conclusion Our findings identify a novel subpopulation of B-1 cells that is enriched for autoreactive specificities, undergoes isotype switch, manifests enhanced antigen presentation, promotes Th17 cell differentiation, and is preferentially associated with the development of lupus in a murine model. Together, these findings suggest that L2pB1 cells have the potential to initiate autoimmunity through serologic and T cell,mediated mechanisms. [source]


CXCL12 Is a constitutive and inflammatory chemokine in the intestinal immune system

INFLAMMATORY BOWEL DISEASES, Issue 4 2010
Iris Dotan MD
Abstract Background: Inflammatory bowel disease (IBD) is characterized by increased lymphocytic infiltrate to the lamina propria (LP) and upregulation of inflammatory chemokines and receptors. CXCL12 is a constitutive chemokine involved in lung, brain, and joint inflammation. We hypothesized that CXCL12 and its receptor, CXCR4, would have a constitutive and inflammatory role in the gut. Methods: Intestinal epithelial cells (IECs) and T lymphocytes were isolated from intestinal mucosa of IBD and control patients undergoing bowel resection. Autologous T cells were isolated from peripheral blood (PB). CXCL12 and CXCR4 expression by IECs was assessed by polymerase chain reaction and immunohistochemistry, lymphocyte phenotype by flow cytometry, and migration by Transwells. Results: IECs expressed CXCL12 and expression was increased and more diffuse in IBD compared to normal crypts (ulcerative colitis [UC] > Crohn's disease [CD], inflamed > noninflamed). CXCR4 was expressed by IECs, LP T cells (LPTs), and PB T cells (PBTs), and CXCR4+ cells were increased in IBD LP in situ. PBTs and LPTs from all patients had a high and comparable migration toward CXCL12 (P < 0.0001 and P < 0.05 vs. medium, respectively). Migration toward IBD-IEC-derived supernatant was significantly higher compared to normal. Antibodies against CXCR4 and CXCL12 blocked migration. Conclusions: CXCL12 is expressed by normal IECs and upregulated and differentially distributed in IBD IECs. CXCR4 is expressed by IECs and LPTs, and CXCR4+ cells are significantly increased in IBD LP. CXCL12 is chemotactic for both PBTs and LPTs. Thus, CXCL12 and CXCR4 have a constitutive and inflammatory role in the intestinal mucosa and their selective therapeutic manipulation may be considered in IBD management. (Inflamm Bowel Dis 2009;) [source]


Constitutive overexpression of BAFF in autoimmune-resistant mice drives only some aspects of systemic lupus erythematosus,like autoimmunity

ARTHRITIS & RHEUMATISM, Issue 8 2010
William Stohl
Objective To determine whether overexpression of BAFF can promote systemic lupus erythematosus (SLE),like autoimmunity in mice that are otherwise autoimmune-resistant. Methods We used class II major histocompatibility complex (MHC),deficient C57BL/6 (B6) mice as a model of resistance to SLE and Sles1 -bearing B6 mice as a model of resistance to the autoantibody-promoting capacity of the Sle1 region. We generated BAFF-transgenic (Tg) counterparts to these respective mice and evaluated lymphocyte phenotype, serologic autoimmunity, renal immunopathology, and clinical disease in the BAFF-Tg and non-Tg mouse sets. Results Although constitutive BAFF overexpression did not lead to B cell expansion in class II MHC,deficient B6 mice, it did lead to increased serum IgG autoantibody levels. Nevertheless, renal immunopathology was limited, and clinical disease did not develop. In B6 and B6.Sle1 mice, constitutive BAFF overexpression led to increased numbers of B cells and CD4+ memory cells, as well as increased serum IgG and IgA autoantibody levels. Renal immunopathology was modestly greater in BAFF-Tg mice than in their non-Tg counterparts, but again, clinical disease did not develop. Introduction of the Sles1 region into B6.Sle1.Baff mice abrogated the BAFF-driven increase in CD4+ memory cells and the Sle1 -driven, but not the BAFF-driven, increase in serum IgG antichromatin levels. Renal immunopathology was substantially ameliorated. Conclusion Although constitutive BAFF overexpression in otherwise autoimmune-resistant mice led to humoral autoimmunity, meaningful renal immunopathology and clinical disease did not develop. This raises the possibility that BAFF overexpression, even when present, may not necessarily drive disease in some SLE patients. This may help explain the heterogeneity of the clinical response to BAFF antagonists in human SLE. [source]


CD4 lymphopenia as a risk factor for febrile neutropenia and early death after cytotoxic chemotherapy in adult patients with cancer

CANCER, Issue 11 2004
Christophe Borg M.D.
Abstract BACKGROUND Lymphopenia is frequently observed in patients with cancer and correlates with the risk of febrile neutropenia and early death after chemotherapy. The phenotype of the depleted lymphocyte populations was investigated in the current study. METHODS Peripheral blood lymphocyte subsets (CD3, CD4, CD8, CD19, CD56) were quantified on Day 1 using fluorescence-activated cell sorting in a prospective study of 213 patients with cancer treated with chemotherapy in a single oncology ward during 12 months. Correlations between lymphocyte phenotype, clinical characteristics, and the risk of febrile neutropenia and early death within 31 days after chemotherapy were investigated in univariate and multivariate analyses. RESULTS Total lymphocyte count and CD3, CD4, and CD8 lymphocyte subsets were significantly lower in patients who experienced febrile neutropenia. Total lymphocyte count and CD3, CD4, CD8, CD19, and CD56 lymphocyte subsets were significantly lower in patients who died within 31 days after chemotherapy. Using logistic regression, CD4 lymphopenia (< 450/,L; odds ratio [OR] = 2.9, 95% confidence interval [CI] = 1.5,5.9) and the dose of chemotherapy (OR = 3,9, 95% CI = 2.0,7.8) were both identified as independent risk factors for febrile neutropenia. Fifty-four percent of patients with both risk factors experienced febrile neutropenia. CD4 lymphocyte count < 450/,L was also an independent risk factor for early death (OR = 7.7, 95% CI = 1.7,35). Thirteen percent of patients with a CD4 lymphocyte count , 450/,L died within 31 days after chemotherapy. Eighty-seven percent (14 of 16) of patients who died before Day 31 had a CD4 lymphocyte count < 450/,L. CONCLUSIONS A low CD4 count was an independent risk factor for febrile neutropenia and early death in patients receiving cytotoxic chemotherapy. Cancer 2004. © 2004 American Cancer Society. [source]


Inflammatory changes associated with circadian variation in pulmonary function in subjects with mild asthma

CLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2004
E. A. B. Kelly
Summary Background Nocturnal enhancement of airway inflammation has been demonstrated in patients with asthma who have a significant drop in pulmonary function at night. Objective To investigate the circadian changes in airway inflammation and their relationship with variations in pulmonary function in subjects with mild atopic asthma. Methods Twelve asthma subjects were admitted to the hospital for two separate 24-h visits. Bronchoalveolar lavage (BAL) was performed at 04:00 hours during one visit, and at 16:00 hours during another visit. BAL cells were analysed for lymphocyte phenotype and the capacity to secrete cytokines following ex vivo stimulation with phytohaemagglutinin (PHA). Results The numbers of BAL lymphocytes and the percentage of CD4+ T cells were higher at 04:00 hours compared with 16:00 hours. At 04:00 hours, the forced expiratory volume in 1 s (FEV1) was inversely correlated with BAL lymphocytes and CD4+ cells. PHA-induced generation of IL-5 by BAL cells correlated with BAL eosinophils and CD4+ cells. Moreover, there was a linear relationship between the relative change (16:00,04:00 hours) in IL-5 and circadian variation in FEV1. Conclusions These data suggest that the circadian variation in lung function in asthma is associated with increased airway CD4+ lymphocyte numbers and their capacity to generate IL-5. Furthermore, in mild asthma, these circadian changes appear to fall into a continuous range, suggesting that day/night variations in airway inflammation and lung function occur on a continuum, rather than as an all-or-none phenomenon. [source]


Treadmill exercise in mice increases intestinal lymphocyte loss via apoptosis

ACTA PHYSIOLOGICA, Issue 3 2003
L. Hoffman-Goetz
Abstract Strenuous exercise is associated with a transient decline in circulating lymphocytes, possibly through increased apoptosis. Intestinal lymphocytes are important effector cells of intestinal immune function but have not been studied in relation to exercise. Aim:, The purpose of the present study was to examine the effect of exercise on intestinal lymphocyte phenotypes and apoptosis. Methods:, Female C57BL/6 mice (n = 112) were randomized to: (1) treadmill running (90 min, 32 m min,1, 8° grade) and killed immediately after exercise, (2) treadmill running and killed 2 h after exercise, (3) treadmill running and killed 24 h after exercise or (4) a non-exercised control condition with exposure to treadmill noise and vibration without running. Results:, Flow cytometry indicated that the total intestinal CD3+T (P < 0.01), CD4+T (P < 0.005), CD8+T (P < 0.05), pan-NK (P < 0.005) and CD19+B (P < 0.05) lymphocytes were significantly lower 24 h after exercise compared with non-exercised controls. Significantly more CD3+T (P < 0.05) and CD8+T (P < 0.05) intestinal lymphocytes stained positive for annexin V, a marker of apoptosis, at 24 h after exercise compared with intestinal lymphocytes from non-exercised controls. Plasma corticosterone and 8-isoprostane concentrations were also significantly higher immediately after exercise compared with other exercise conditions. Conclusion:, Acute strenuous exercise increases intestinal T (CD3+ and CD8+) lymphocyte loss and apoptosis. The extent to which the exercise-induced apoptosis in intestinal lymphocytes is mediated by increased glucocorticoid concentrations in the gastrointestinal tract will require further studies. [source]