Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Though lymphopenia is often noted in malnourished humans and rodents, little is known about the effects of suboptimal nutriture on lymphopoietic processes. Focusing primarily on cells of the B lineage in the marrow of young adult mice, a moderate degree of zinc deficiency (MZD) caused a 43% decline in the proportion of nucleated cells bearing B220 with a 91% decline noted among more severely zinc deficient mice (SZD). Early B cells (B220+Ig-) were highly sensitive to the deficiency, being barely detectable in SZD mice and reduced by almost 60% in MZD mice. Immature B cells (B220+IgM+IgD-) were similarly affected, declining 35% to 80% depending on the degree of the deficiency. In MZD mice, mature B cells (IgM+IgD+) exhibited moderate losses, being somewhat resistant. A more profound loss in this population was noted for SZD mice. Flow cytometric (FACS) scatter profiles indicated that zinc deficiency caused a sharp decline in the proportion of small nucleated cells which in the marrow are thought to contain a high proportion of developing lymphoid cells. There was a concomitant increase in large granular cells that paralleled a substantial increase in the proportion of nucleated cells bearing Mac-1 for both MZD and SZD mice. Given the dramatic depletion of cells of the B lineage in the marrow created by a deficiency in zinc, it is probable that disruptions in lymphopoietic processes in the marrow play a key role in the resulting lymphopenia observed in many types of malnutrition.
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PMID:Depletion of cells of the B lineage in the bone marrow of zinc-deficient mice. 763 24

We investigated whether, in systemic lupus erythematosus (SLE), the CD45 isoforms expression on peripheral blood T-lymphocytes (T-PBL) is related to the auto-immune processes and hematological manifestations. The CD45RA/RO patterns of CD4+ and CD8 bright+ T-PBL were determined by three-colour flow cytometry. The serum levels of anti-nuclear (ANA), anti-double stranded DNA (ds DNA) and anti-cardiolipin (CL) autoantibodies were quantified by ELISA. The hematological parameters were routinely assessed. 72% of SLE patients (n = 29) had reduced lymphocyte counts, which correlated with more severe physician's assessment of disease activity, increased ANA and anti-ds DNA auto-antibodies. The lymphopenia preferentially affected the CD4+ T-PBL and, among them, the "naive" CD45RA+, RO- cells. Thus, compared with healthy women (n = 29), SLE patients had less naive and more "transient" CD45RA+, RO+ cells among CD4+ T-PBL. Meanwhile, on average, the CD45 isoforms expression on CD8+ T-PBL was unchanged. Interestingly, in 3 patients who were repeatedly evaluated, increases of transient CD8+ T-PBL paralleled the elevation of anti-ds DNA. In addition, high anti-CL was associated with more transient CD4+ and CD8+ T-PBL. The loss of naive and increase of transient CD8+ T-PBL was associated with increased disease activity and possibly hemolytic anemia. Thus, in SLE, the enhanced phenotypic switch from naive CD45RA+, RO- to "memory" CD45RO+ T-PBL patterns paralleled the auto-immune processes characteristic of this disease.
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PMID:CD45 isoforms expression on CD4+ and CD8+ peripheral blood T-lymphocytes is related to auto-immune processes and hematological manifestations in systemic lupus erythematosus. 894 97

We investigated the role of IL-7 receptor alpha (IL-7Ralpha) signal in the formation of Peyer's patch (PP) anlage. Although pan-lymphopenia is a common phenotype of rag2-/- and il7ralpha-/- mice, a close inspection revealed nodules corresponding to PP in the adult rag2-/- but not in the il7ralpha-/- mouse. In our previous study, three histologically distinct steps in the formation of PP were identified. The first is the appearance of VCAM-1 + spots in the intestine, which probably represents an initial stage of the formation of the PP anlage. Accumulation of cells bearing IL-7Ralpha, CD4 or Ia in this region then follows and eventually entry of mature lymphocytes expressing CD3 or B220 occurs just before birth. Based on this criterion, we next investigated which of these events is defective in mice with severe combined immunodeficiency. Formation of VCAM-1 + spots and cluster formation of IL-7Ralpha+ cells proceed normally in the rag2-/- mouse which completely lacks mature lymphocytes. In contrast, no VCAM-1+ spots were detected in the embryonic nor neonatal il7ralpha-/- mice, suggesting that IL-7Ralpha signal is involved in the early phase of PP anlage formation. The same defect was found in the jak3-/- mouse. In addition to the appearance of VCAM1+ spots, the clustering of IL-7Ralpha+ cells was absent in the jak3-/- mouse, though IL-7Ralpha+ cells are found to scatter over the intestine. These results indicate that IL-7Ralpha is an essential signal for an early step of PP anlage formation, without which the subsequent processes cannot be initiated.
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PMID:Essential role of IL-7 receptor alpha in the formation of Peyer's patch anlage. 948 50

Most cytotoxic drugs have gross effects on the immune system, such as neutropenia and lymphopenia. However, their effects on tumor-specific immune responses are unknown. Gemcitabine is a nucleoside analogue that is frequently used to treat non-small cell lung cancer. It is also active in other malignancies, either alone or in combination with cisplatin. Here, we investigate its effects on antigen-specific antitumor immunity using a murine tumor cell line transfected to express influenza virus hemagglutinin (HA). CD4(+), CD8(+), and B220(+) lymphocyte numbers all decreased during chemotherapy (120 microg/g, i.p., every third day for five doses), but B cells were selectively depleted. Gemcitabine induced a profound suppression of the IgG antibody response to HA, and this was unrelated to tumor size. In contrast, in vitro T-lymphocyte recall responses to the class I- and class II-restricted dominant peptide epitopes of HA were enhanced in tumor-bearing, gemcitabine-treated mice. We found that gemcitabine was >2-fold more potent in its ability to inhibit B-lymphocyte proliferation compared with T-lymphocyte proliferation. Thus, gemcitabine does not appear to be detrimental to specific antitumor cellular immunity and may be useful in combination chemo-immunotherapy protocols. In contrast, vaccination protocols requiring a humoral immune response for maximal efficacy may be compromised in patients treated with gemcitabine.
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PMID:Gemcitabine exerts a selective effect on the humoral immune response: implications for combination chemo-immunotherapy. 1195 96

The aim of this paper was to compare the effect of flumethasone and meloxicam in combination with oxytetracycline on clinical and immunological parameters of calves suffering from enzootic bronchopneumonia. The study was performed on 30 Black-and-White Lowland Breed calves with clinical signs of enzootic bronchopneumonia divided randomly into three equal groups and, respectively, treated with-Group I: oxytetracycline and meloxicam; Group II: oxytetracycline and flumethasone; Group III (control): oxytetracycline only. Treatment of calves with the combination of oxytetracycline and meloxicam (Group I) caused a significantly faster, in comparison to other groups, improvement in the clinical illness index score (CIIS: cough, nasal discharge, dyspnea, depression and anorexia) and a faster normalization of body temperature. A slow decrease in white blood cell (WBC) count, the number of neutrophils, MID (mixed number of monocytes, eosinophils and basophils) and in the individual number of monocytes (CD14/CD45 positive cells) was observed in Groups I and III. In the blood of the calves which received oxytetracycline and flumethasone (Group II), leukocytosis, neutrophilia and monocytosis with concomitant lymphopenia and a low number of T cells (CD2+) was observed. Moreover, the calves treated with flumethasone exhibited a decrease in gamma-globulin concentration, and phagocytic parameters. Both drugs, flumethasone and meloxicam slightly decreased tumor necrosis factor (TNF) but meloxicam slightly increased the levels of interferon (IFN) in sera and in bronchoalveolar lavages (BALs). These results suggest that the combination of meloxicam with an antibiotic in calves suffering from enzootic bronchopneumonia is superior to the antibiotic alone and also to the combination of the antibiotic with flumethasone.
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PMID:Effect of steroidal and non-steroidal anti-inflammatory drugs in combination with long-acting oxytetracycline on non-specific immunity of calves suffering from enzootic bronchopneumonia. 1451 8

Severe combined immunodeficiency (SCID) is an inherited immune disorder characterized by T-cell lymphopenia (TCLP), a profound lack of cellular (T-cell) and humoral (B-cell) immunity and, in some cases, decreased NK-cell number and function. Affected children develop severe bacterial and viral infections within the first 6 months of life and die before 1 year of age without treatment. Mutations in any of eight known genes: IL2RG, ARTEMIS, RAG1, RAG2, ADA, CD45, JAK3, and IL7R cause SCID. Mutations in unidentified genes may also cause SCID. Population-based genotype and allelic frequencies of these gene defects have not been measured. Some minimal estimates of SCID prevalence are presented. Currently, hematopoietic stem cell transplants are the standard treatment. In clinical trials, gene therapy has been used to reconstitute immune function in patients with IL2RG and ADA defects. The availability of effective therapies, plus the short asymptomatic period after birth, (when stem-cell transplantation is most effective), make SCID a potentially good candidate for newborn screening. Dried blood spots are currently collected from all infants at birth for newborn metabolic screening. Tests for TCLP on dried blood spots could be developed as a screen for SCID. Because SCID may be unrecognized, with infant deaths from infection attributed to other causes, newborn screening is the only way to ascertain true birth prevalence. Validated tests and pilot population studies are necessary to determine newborn screening's potential for identifying infants with SCID.
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PMID:Mutations in genes required for T-cell development: IL7R, CD45, IL2RG, JAK3, RAG1, RAG2, ARTEMIS, and ADA and severe combined immunodeficiency: HuGE review. 1472 5

We investigated the changes in percentages of leukocyte subpopulations, natural killer (NK) cells, CD69-expressing lymphocytes, and psychological aspects in 10 subjects who participated in a 10-day confinement study. Suppression of lymphocyte proliferative reaction and changes in leukocyte distribution are known to occur in space. These responses are similar to those induced by psychological stress. Ground-based confinement studies are suitable for validating the effects of stress arising only due to confinement. Two groups, consisting of five male subjects (ages 20-27 yr, mean 22.8 yr) each, participated in a 10-day confinement study. Blood samples were taken once before, three times during, and once after the confinement and activated with an anti-CD2 agonistic antibody cocktail. The percentages of leukocyte subpopulations, NK (CD45(+)CD56+) cells, and activated lymphocytes (CD45(+)CD69+) were measured by flow cytometric assay. The face scale test was used to measure psychological aspects. The percentage of CD69+ lymphocytes decreased during the period of confinement. This was mostly caused by changes in the ratio between NK and non-NK lymphocytes. The face scale showed that the subjects' moods improved toward the postconfinement period. Consistent with the face scale, the percentages of innate immune cells, such as NK cells and granulocytes, increased during the postconfinement period. We concluded that the changes in the distribution of immune cells caused by stress plays an important role in suppression of proliferative reactivity. The observed physiological reactions were specific to the confined environment, and the stress caused by confinement plays a role in the immune changes observed in space.
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PMID:Effects of 10-day confinement on the immune system and psychological aspects in humans. 1514 27

The function of the Src-family kinases (SFKs) Lck and Fyn in T cells has been intensively studied over the past 15 years. Animal models and cell line studies both indicate a critical role for Lck and Fyn in proximal T-cell antigen receptor (TCR) signal transduction. Recruited SFKs phosphorylate TCR ITAMs (immunoreceptor tyrosine-based activation motifs) in the CD3 and zeta chains, which then serve as docking sites for Syk-family kinases. SFKs then phosphorylate and activate the recruited Syk-family kinase. Lck and Fyn are spatially segregated in cell membranes due to differential lipid raft localization, and may undergo sequential activation. In addition to the CD4 and CD8 coreceptors, a recently described adaptor, Unc119, may link SFKs to the TCR. CD45 and Csk provide positive and negative regulatory control of SFK functions, respectively, and Csk is constitutively bound to the transmembrane adapter protein, PAG/Cbp. TCR-based signaling is required at several stages of T-cell development, including at least pre-TCR signaling, positive selection, peripheral maintenance of naive T cells, and lymphopenia-induced proliferation. SFKs are required for each of these TCR-based signals, and Lck seems to be the major contributor.
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PMID:Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. 1548 16

A boy with lifelong recurrent bacterial infection at cutaneous and mucosal sites was investigated. PMN oxidative burst to phorbol myristate acetate (PMA) and zymosan was normal but was increased 20- to 50-fold upon C5a or formyl-met-leu-phe (fMLP) chemoattractant stimulation, accompanied by accelerated PMN apoptosis. His PMNs showed increased constitutive tyrosine phosphorylation of 21-, 25-, and 44-kDa proteins, and of src-family kinases (p59(hck), p58(fgr), and p53/56(lyn)). Phosphorylation was abnormally enhanced following fMLP stimulation. Expression and activity of the major PMN tyrosine phosphatases, i.e., CD45, CD148, and SHP-1 and -2, was normal. However, dephosphorylation of phospho-p58(fgr) and phospho-p53/56(lyn) by lysates of patient's PMNs was enhanced. Thus, another phosphatase may be overactive, perhaps dephosphorylating a regulatory (inhibitory) site on a protein tyrosine kinase, accounting for the abnormal PMN tyrosine phosphorylation and function. With age (now 13 years), T-cell lymphopenia and loss of T-cell responses developed. This appears to be a unique primary immunodeficiency with abnormal PMN oxidative and apoptotic responses to chemoattractants, dysregulated protein tyrosine phosphorylation, serious bacterial infection, and T-lymphocyte attrition.
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PMID:Increased chemoattractant induced neutrophil oxidative burst, accelerated apoptosis, and dysregulated tyrosine phosphorylation associated with lifelong bacterial infections. 1601 63

The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency syndrome caused by mutations in the WAS protein (WASP). This participates in signalling and cytoskeletal homoeostasis, and some of its activities are regulated by its binding to the WASP interacting protein (WIP). WIP deficiency, however, has not yet been shown to be of pathological significance in humans. Here we show that, in WIP null (WIP(-/-)) mice, it produces haematological alterations and anatomical abnormalities in several organs, most probably as a consequence of autoimmune attacks. Granulocytosis and severe lymphopenia are associated with a proportional increase in segmented cells and fewer bone marrow erythrocytes and lymphocytes. Splenomegaly is accompanied by an increase of haematopoietic tissue and red pulp, reduction of the white pulp, and fewer B (B220(+)) lymphocytes (also apparent in the lymph nodes and Peyer's patches). Ulcerative colitis, interstitial pneumonitis, glomerular nephropathy with IgA deposits, autoantibodies, and joint inflammation are also evident. These progressive immunological disorders closely mimic those seen in WAS. WIP deficiency may thus be implicated in some cases in which mutations in the gene encoding WASP are not detected.
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PMID:WIP null mice display a progressive immunological disorder that resembles Wiskott-Aldrich syndrome. 1708 54


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