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Lymphocyte Numbers (lymphocyte + number)
Selected AbstractsBlood basophil numbers in chronic ordinary urticaria and healthy controls: diurnal variation, influence of loratadine and prednisolone and relationship to disease activityCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2003C. E. H. Grattan Summary Background The basopenia of chronic urticaria relates to histamine releasing autoantibodies in the serum of patients with autoimmune urticaria. This reduction in circulating basophils may be due to active recruitment into weals. If so, it might be expected that numbers in blood would be reduced when urticaria is active and increased after treatment. The primary aim of this study was to look at diurnal variation of basophil numbers in patients with chronic ordinary urticaria (not physical or vasculitic) in relation to disease activity and the effect of treatment with antihistamines and corticosteroids, and to compare the results with healthy controls. A secondary aim was to compare a standard manual counting method with automated basophil counts and to look at numbers of other circulating leucocytes that might be relevant to urticaria pathogenesis. Methods Manual basophil counts using a toluidine blue stain and automated 5-part differentials (Coulter® Gen. SÔ) were performed at 4-hourly intervals from 08.00 to 20.00 in 10 healthy controls (six women, age 24 to 63 years) and seven chronic urticaria patients (five women, 24 to 50 years). All chronic urticaria patients had severe daily or almost daily urticaria. Only one of six chronic urticaria sera showed in vitro basophil histamine releasing activity. Counts were performed without treatment, after a week of taking loratadine 10 mg daily and after 3 days of adding prednisolone at 0.6 mg/kg/day (maximum 40 mg). Daily urticarial activity scores (UAS) were derived from weal numbers and itch, maximum 7. Results There was no significant overall diurnal variation of basophil numbers in healthy controls or chronic urticaria patients. Mean (SE) manually counted basophil were higher in healthy controls than chronic urticaria (43.4/µL (2.1) vs. 4.4 (0.8), P < 0.001). Basophil counts were reduced in healthy controls on steroids (19.2 (1.9), P < 0.001) but increased in chronic urticaria (8.9 (1.9), P < 0.001). Loratadine did not influence them. UAS fell on treatment (3.3 (0.4) baseline, 1.4 (0.5) on loratadine and 0.5 (0.2) on prednisolone with loratadine, P < 0.001). There was a negative linear correlation between basophil numbers and UAS in untreated chronic urticaria patients (P = 0.001, Spearman rank correlation). Manual and automated basophil counts showed poor agreement. Lymphocyte numbers were lower in chronic urticaria than healthy controls. Neutrophils increased whereas lymphocytes and eosinophils decreased in all subjects on prednisolone. They were unaffected by loratadine. Conclusion The results are consistent with the hypothesis that circulating basophils may be recruited from blood into urticarial weals during disease activity. Automated counts are not suitable for assessing basophil numbers in chronic urticaria. The relevance of reduced lymphocyte numbers in chronic urticaria needs to be explored. [source] Effect of in vitro and in vivo organotin exposures on the immune functions of murray cod (Maccullochella peelii peelii)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2007Andrew J. Harford Abstract Murray cod (Maccullochella peelii peelii) is an iconic native Australian freshwater fish and an ideal species for ecotoxicological testing of environmental pollutants. The species is indigenous to the Murray-Darling basin, which is the largest river system in Australia but also the ultimate sink for many environmental pollutants. The organotins tributyltin (TBT) and dibutyltin (DBT) are common pollutants of both freshwater and marine environments and are also known for their immunotoxicity in both mammals and aquatic organisms. In this study, TBT and DBT were used as exemplar immunotoxins to assess the efficiency of immune function assays (i.e., mitogen-stimulated lymphoproliferation, phagocytosis in head kidney tissue, and serum lysozyme activity) and to compare the sensitivity of Murray cod to other fish species. The organotins were lethal to Murray cod at concentrations previously reported as sublethal in rainbow trout (i.e., intraperitoneal [i.p.] lethal dose to 75% of the Murray cod [LD75] = 2.5 mg/kg DBT and i.p. lethal dose to 100% of the Murray cod [LD100] = 12.5 mg/kg TBT and DBT). In vivo TBT exposure at 0.1 and 0.5 mg/kg stimulated the phagocytic function of Murray cod (F = 6.89, df = 18, p = 0.004), while the highest concentration of 2.5 mg/kg TBT decreased lymphocyte numbers (F = 7.92, df = 18, p = 0.02) and mitogenesis (F = 3.66, df = 18, p = 0.035). Dibutyltin was the more potent immunosuppressant in Murray cod, causing significant reductions in phagocytic activity (F = 5.34, df = 16, p = 0.013) and lymphocyte numbers (F = 10.63, df = 16, p = 0.001). [source] Methylenedioxymethamphetamine (MDMA, ,Ecstasy'): a stressor on the immune systemIMMUNOLOGY, Issue 4 2004Thomas J. Connor Summary Drug abuse is a global problem of considerable concern to health. One such health concern stems from the fact that many drugs of abuse have immunosuppressive actions and consequently have the potential to increase susceptibility to infectious disease. This article is focused on the impact of the amphetamine derivative, methylenedioxymethamphetamine (MDMA; ,Ecstasy') on immunity. Research conducted over the last 5 years, in both laboratory animals and humans, has demonstrated that MDMA has immunosuppressive actions. Specifically, MDMA suppresses neutrophil phagocytosis, suppresses production of the pro-inflammatory cytokines tumour necrosis factor-, (TNF-,) and interleukin (IL)-1,, and increases production of the endogenous immunosuppressive cytokine (IL-10), thereby promoting an immunosuppressive cytokine phenotype. MDMA also suppresses circulating lymphocyte numbers, with CD4+ T cells being particularly affected, and alters T-cell function as indicated by reduced mitogen-stimulated T-cell proliferation, and a skewing of T-cell cytokine production in a T helper 2 (Th2) direction. For the most part, the aforementioned effects of MDMA are not the result of a direct action of the drug on immune cells, but rather caused by the release of endogenous immunomodulatory substances. Consequently, the physiological mechanisms that are thought to underlie the immunosuppressive effects of MDMA will be discussed. As many of the physiological changes elicited by MDMA closely resemble those induced by acute stress, it is suggested that exposure to MDMA could be regarded as a ,chemical stressor' on the immune system. Finally, the potential of MDMA-induced immunosuppression to translate into significant health risks for abusers of the drug will be discussed. [source] Therapeutic benefit of pentostatin in severe IL-10,/, ColitisINFLAMMATORY BOWEL DISEASES, Issue 7 2008Jeffrey B. Brown MD Abstract Background: Pentostatin, an adenosine deaminase (ADA) inhibitor, is a purine antimetabolite used for the treatment of leukemias. ADA inhibition blunts expansion of proliferating lymphocytes and increases adenosine release, a potent anti-inflammatory molecule. Human inflammatory bowel disease (IBD) is driven by expansion of effector T cells (Teff) that overwhelm reulatory T cells (Treg) and propagate innate immune reponses. Here we study the therapeutic benefits of ADA inhibition to impair Teff cell expansion and reduce inflammatory cytokine release in IL-10-deficient (IL-10 -/- ) mice. Methods: Colitis was induced in IL-10 -/- mice by administering piroxicam for two weeks. Mice were treated with daily pentostatin or phosphate-buffered saline for 1 week and effects on tissue inflammation, lymphocyte numbers and cytokine production examined. Results: Pentostatin reduced inflammation by >50% and nearly normalized serum amyloid A levels. Lymphocyte expansions in the colon and mesenteric lymph node (MLN) (3.5-fold and >5-fold respectively) dropped by >50-90%. Pro-inflammatory factors in the colon and MLN (IL-1,, IFN-,, IL-6, CXCL10, TNF) dropped whereas FoxP3 and TGF-, were unchanged. Reductions in cytokine production from equivalent numbers of T cells from pentostatin-treated mice after in vitro (36h) or in vivo (3h) activation suggested anti-inflammatory effects of pentostatin independent of lymphodepletion contributed to its therapeutic benefit. Analysis of mucosal lymphocyte subsets suggested pentostatin reduced numbers of effector CD4+ CD69+ T cells, while sparing CD4+ CD62L+ T cells. Conclusions: Pentostatin dosages that avoid severe lymphocyte depletion effectively treat colitis by impairing Teff cell expansion and reducing pro-inflammatory cytokine production while preserving regulatory Treg populations and function. (Inflamm Bowel Dis 2008) [source] Suppression of hepatocellular carcinoma by transplantation of ex-vivo immune-modulated NKT lymphocytesINTERNATIONAL JOURNAL OF CANCER, Issue 3 2005Maya Margalit Abstract NKT cells are a regulatory subset of T lymphocytes with immune modulatory effects and an important role in anti-tumor immunity. The feasibility of "ex-vivo education" of NKT cells has recently been demonstrated. To evaluate the anti-tumor effect of ex-vivo immune-modulated NKT lymphocytes in a murine model of hepatocellular carcinoma. Athymic Balb/C mice were sublethally irradiated and transplanted with human Hep3B HCC. NKT cells prepared from immunocompetent Balb/C mice were pulsed ex vivo with HCC-derived antigens (Group A), Hep3B cells (group B) or BSA (group C), and adoptively transferred into HCC harboring mice (1 × 06 NKT cells per mouse). Group D mice did not undergo NKT cell transplantation. Group E mice were transplanted with 1 × 106 NKT cells from HBV-immunized donors. Mice were followed for tumor size and weight. To determine the mechanism of the anti-tumor effect, intrasplenic lymphocyte populations were analyzed by FACS for NKT, CD4+ and CD8+ lymphocyte subpopulations; STAT 1, 4 and 6 expression in splenocytes was assessed by Western blot, and serum cytokine levels were measured by ELISA. Adoptive transfer of NKT cells pulsed with HCC-derived antigens (group A) and NKT cells from immunized donors (group E) resulted in complete disappearance of tumors within 4 weeks and attenuated weight loss (6.5% and 7% in groups A and E, respectively). In contrast, mice in groups B, C, and D developed large, necrotic tumors and severe weight loss (21%, 17% and 23% weight loss in groups B, C, and D, respectively). NKT/CD4 and CD8/CD4 ratios were significantly increased in groups A and E (12.3 and 17.6 in groups A and D, respectively, compared to 6.4, 4.8 and 5.6 in groups B, C and D, respectively, for the NKT/CD4 ratio; 41 and 19.8 in groups A and E, respectively, compared to 6.5, 11.8 and 3.2 in groups B, C, and D, respectively, for the CD8/CD4 ratio). Expression of the transcription factor STAT4 was evident in group A, but not in groups B-D. Serum IFN,, IL12 and IL4 levels were increased in groups A and E. Adoptive transfer of NKT lymphocytes exposed ex vivo by HCC-derived antigens loaded on dendritic cells and NKT cells from immunized donors led to suppression of HCC in mice. NKT-mediated anti-tumor activity was associated increased NKT and CD8+ T lymphocyte numbers, increased expression of STAT4, a marker for IL-12 activity and elevated serum levels of the proinflammatory cytokines IFN, and IL12, and of IL4. Ex-vivo modulation of NKT lymphocytes holds promise as a novel mode of immune therapy for HCC. © 2005 Wiley-Liss, Inc. [source] Influence of anesthesia on immune responses and its effect on vaccination in children: review of evidencePEDIATRIC ANESTHESIA, Issue 5 2007J.N. SIEBERT MD Summary Anesthesia and surgery exert immunomodulatory effects and some authors argue that they may exert additive or synergistic influences on vaccine efficacy and safety. Alternatively, inflammatory responses and fever elicited by vaccines may interfere with the postoperative course. There is a lack of consensus approach among anesthesiologists to the theoretical risk of anesthesia and vaccination. Few studies have assessed the influence of anesthesia and surgery on pediatric vaccine responses. We have undertaken an extensive review of articles published in English between 1970 and 2006 meeting the criteria: measurement of immune parameters following general anesthesia in children. By searching the major medical databases (OVID Medline, PubMed, ISI Web of Science) and references cited in the articles themselves, among 277 articles obtained none examined directly the influence of anesthesia/surgery on vaccine responses. Only 16 original reports assessed the influence of several anesthetic agents on various markers of immunity including lymphocyte numbers and functions. These results are reinterpreted here in view of our current understanding of the immune mechanisms underlying vaccine efficacy and adverse events. We conclude that the immunomodulatory influence of anesthesia during elective surgery is both minor and transient (around 48 h) and that the current evidence does not provide any contraindication to the immunization of healthy children scheduled for elective surgery. However, respecting a minimal delay of 2 days (inactivated vaccines) or 14,21 days (live attenuated viral vaccines) between immunization and anesthesia may be useful to avoid the risk of misinterpretation of vaccine-driven adverse events as postoperative complications. [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] Blockade of Macrophage Colony-Stimulating Factor Reduces Macrophage Proliferation and Accumulation in Renal Allograft RejectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2003Matthew D. Jose Macrophage accumulation within an acutely rejecting allograft occurs by recruitment and local proliferation. To determine the importance of M-CSF in driving macrophage proliferation during acute rejection, we blocked the M-CSF receptor, c-fms, in a mouse model of acute renal allograft rejection. C57BL/6 mouse kidneys (allografts, n = 20) or BALB/c kidneys (isografts, n = 5) were transplanted into BALB/c mice. Anti-c-fms antibody (AFS98) or control Ig (50 mg/kg/day, i.p.) was given daily to allografts from days 0,5. All mice were killed day 6 postoperatively. Expression of the M-CSF receptor, c-fms, was restricted to infiltrating CD68+ macrophages. Blockade of c-fms reduced proliferating (CD68+/BrdU+) macrophages by 82% (1.1 v 6.2%, p < 0.001), interstitial CD68+ macrophage accumulation by 53% (595 v 1270/mm2, p < 0.001), and glomerular CD68+ macrophage accumulation by 71% (0.73 V 2.48 CD68+ cells per glomerulus, p < 0.001). Parameters of T-cell involvement (intragraft CD4+, CD8+ and CD25+ lymphocyte numbers) were not affected. The severity of tubulointerstitial rejection was reduced in the treatment group as shown by decreased tubulitis and tubular cell proliferation. Macrophage proliferation during acute allograft rejection is dependent on the interaction of M-CSF with its receptor c-fms. This pathway plays a significant and specific role in the accumulation of macrophages within a rejecting renal allograft. [source] Decreased immunocompetence in a severely bottlenecked population of an endemic New Zealand birdANIMAL CONSERVATION, Issue 1 2007K. A. Hale Abstract Inbreeding resulting from severe population bottlenecks may impair an individual's immune system and render it more susceptible to disease. Although a reduced immune response could threaten the survival of highly endangered species, few studies have assessed the effect of population bottlenecks on immunocompetence. We compared the counts of leucocytes and external, blood and gastrointestinal parasite loads in two populations of the endemic New Zealand robin Petroica australis to assess the immunocompetence of birds in a severely bottlenecked population relative to its more genetically diverse source population. Despite similar parasite loads in both populations, robins in the severely bottlenecked population showed lower counts of both total leucocyte and total lymphocyte numbers. When the immune system was experimentally challenged using the phytohaemagglutinin skin test, robins in the severely bottlenecked population exhibited a significantly lower immune response than the source population, suggesting that birds passing through a severe bottleneck have a compromised immunocompetence. Our results confirm that severe bottlenecks reduce the immune response of birds and highlight the need to avoid severe bottlenecks in the recovery programmes of endangered species. [source] Inflammatory changes associated with circadian variation in pulmonary function in subjects with mild asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2004E. 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] Blood basophil numbers in chronic ordinary urticaria and healthy controls: diurnal variation, influence of loratadine and prednisolone and relationship to disease activityCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2003C. E. H. Grattan Summary Background The basopenia of chronic urticaria relates to histamine releasing autoantibodies in the serum of patients with autoimmune urticaria. This reduction in circulating basophils may be due to active recruitment into weals. If so, it might be expected that numbers in blood would be reduced when urticaria is active and increased after treatment. The primary aim of this study was to look at diurnal variation of basophil numbers in patients with chronic ordinary urticaria (not physical or vasculitic) in relation to disease activity and the effect of treatment with antihistamines and corticosteroids, and to compare the results with healthy controls. A secondary aim was to compare a standard manual counting method with automated basophil counts and to look at numbers of other circulating leucocytes that might be relevant to urticaria pathogenesis. Methods Manual basophil counts using a toluidine blue stain and automated 5-part differentials (Coulter® Gen. SÔ) were performed at 4-hourly intervals from 08.00 to 20.00 in 10 healthy controls (six women, age 24 to 63 years) and seven chronic urticaria patients (five women, 24 to 50 years). All chronic urticaria patients had severe daily or almost daily urticaria. Only one of six chronic urticaria sera showed in vitro basophil histamine releasing activity. Counts were performed without treatment, after a week of taking loratadine 10 mg daily and after 3 days of adding prednisolone at 0.6 mg/kg/day (maximum 40 mg). Daily urticarial activity scores (UAS) were derived from weal numbers and itch, maximum 7. Results There was no significant overall diurnal variation of basophil numbers in healthy controls or chronic urticaria patients. Mean (SE) manually counted basophil were higher in healthy controls than chronic urticaria (43.4/µL (2.1) vs. 4.4 (0.8), P < 0.001). Basophil counts were reduced in healthy controls on steroids (19.2 (1.9), P < 0.001) but increased in chronic urticaria (8.9 (1.9), P < 0.001). Loratadine did not influence them. UAS fell on treatment (3.3 (0.4) baseline, 1.4 (0.5) on loratadine and 0.5 (0.2) on prednisolone with loratadine, P < 0.001). There was a negative linear correlation between basophil numbers and UAS in untreated chronic urticaria patients (P = 0.001, Spearman rank correlation). Manual and automated basophil counts showed poor agreement. Lymphocyte numbers were lower in chronic urticaria than healthy controls. Neutrophils increased whereas lymphocytes and eosinophils decreased in all subjects on prednisolone. They were unaffected by loratadine. Conclusion The results are consistent with the hypothesis that circulating basophils may be recruited from blood into urticarial weals during disease activity. Automated counts are not suitable for assessing basophil numbers in chronic urticaria. The relevance of reduced lymphocyte numbers in chronic urticaria needs to be explored. [source] | |||||||||||||