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Experiences with thymosin in primary immunodeficiency disease.

Thymosin has no effect in vitro on cyclic AMP levels in thymocytes. However, when thymosin was injected into patients lacking "serum factor" (SF) activity, it induced the appearance of SF or SF-like activity and the disappearance of target cells for SF among the peripheral blood lymphocytes of the treated patients. On the other hand, when thymosin was injected into one patient with normal SF activity, it induced a marked decrease of SF activity and the appearance of target cells for SF among the peripheral blood lymphocytes of this particular patient.

Зависящие от тимуса лимфоциты: уничтожение вирусом лимфоцита.

Выборочное уничтожение небольших лимфоцитов в зависящих от тимуса районах лимфоузлов и тимоцитов было замечено у мышей, инфицированных вирусом лимфоцита. Эти изменения четко проявились в лимфоиде и селезенке через 3 дня после инфекции и в тимусе на 7 день. Разрушительные изменения сопровождали рост вируса в этих органах. Результаты исследования показывают, что инфекция лимфоцита может временно вызвать эквивалентное воздействие неонатальной тимектомии, то есть «вирусной тимектомии», которая, как представляется, связана со способностью этого вируса вызывать стойкую инфекцию.

Совпадение в аннотации оригинала
Selective destruction of small lymphocytes in the thymusdependent areas of lymph nodes and thymocytes was observed in mice infected with lymphocytic choriomeningitis virus. These changes were clearly evident in lymphoid and splenic tissue 3 days after infection and in the thymus by day 7. The destructive changes paralleled growth of the virus in these organs…

Immune-mediated cytopenias in human immunodeficiency virus: the first reported case of idiopathic aplastic anaemia successfully treated with immunosuppression.

Although isolated cytopenias are relatively common in human immunodeficiency virus (HIV), the incidence of aplastic anaemia is extremely rare. We report here the first case of a HIV-infected patient who developed severe idiopathic aplastic anaemia, and who was safely and effectively treated with anti-thymocyte globulin and cyclosporin. We briefly review immune-mediated cytopenias in HIV, including their frequency, pathophysiology and management strategies.

Interleukin-1 in malnutrition.

The effect of malnutrition on the in vitro production of interleukin-1 by lipopolysaccharide stimulated circulating monocytes has been investigated in children suffering from kwashiorkor and marasmus. The interleukin-1 activity was significantly lower in children with severe malnutrition. Furthermore, macrophages from children with kwashiorkor produced factors that suppressed mouse thymocyte proliferation. These observations show a significant impairment of macrophage function and provide a mechanism for the suppression of cellular immunity in malnutrition.

Phase II study of the triple combination of rabbit ATG, ciclosporin and eltrombopag in patients with transfusion-dependent aplastic anaemia: West Japan Hematology Study Group (W-JHS) AA02 trial.

The efficacy of a triple combination of rabbit anti-human thymocyte immunoglobulin (rATG), ciclosporin and eltrombopag (EPAG) was prospectively evaluated in patients with severe or transfusion-dependent non-severe aplastic anaemia (SAA) across 29 institutions in Japan. Sixty patients were enrolled, of whom 48 had SAA. The primary end-point, the haematological overall response rate at 12 weeks, was 52.6% (95% confidence interval, 39.0%-66.0%), increasing to 67.9% at 26 weeks. The most frequent grade 3/4 adverse event was febrile neutropenia (20.0%). One elderly patient with severe neutropenia d

Thymic selection of the T cell receptor repertoire is biased toward autoimmunity in females.

Women represent about 80% of patients with autoimmune diseases. This may partly result from sex-based differences in T cell receptor (TCR) selection during thymocyte development, potentially influenced by hormones and the lower expression of the Autoimmune Regulator (AIRE) transcription factor in females. To investigate this, we analyzed sex-specific differences in TCR generation and selection. We examined TCR repertoires in double-positive thymocytes and single-positive thymic cells, including CD8+ and CD4+ effector T cells and regulatory T cells (Tregs), derived from male and female organ do…

Selective expression of claudin-5 in thymic endothelial cells regulates the blood-thymus barrier and T-cell export.

T-cell development depends on the thymic microenvironment, in which endothelial cells (ECs) play a vital role. Interestingly, vascular perme … ectively into the medulla through the Cld5- vessels, probably ensuring the egress of CD3high mature thymocytes from Cld5- vessels at the CMJ. These results suggest that distinct Cld5 expression profiles in the cortex and medulla may control the BTB and the T-cell gateway to blood circulation, respectively.

The targeting of human and mouse B lymphocytes by dasatinib.

Dasatinib inhibits B-cell receptor-Abelson murine leukemia viral oncogene homologue 1, Src, and other tyrosine kinases. Few studies have add … globulin D(-) B cells and a reduction in germinal center B cells. Dasatinib caused a marked loss of thymocytes without affecting myeloid lineage cells or hematopoietic progenitors. This study reveals important side effects of dasatinib with specific loss of activated B and thymocyte populations, which may have an impact during long-term treatment.

A conserved hydrophobic patch on Vβ domains revealed by TCRβ chain crystal structures: Implications for pre-TCR dimerization.

The αβ T cell receptor (TCR) is a multimeric complex whose β chain plays a crucial role in thymocyte development as well as antigen recognition by mature T lymphocytes. We report here crystal structures of individual β subunits, termed N15β (Vβ5.2Dβ2Jβ2.6Cβ2) and N30β (Vβ13Dβ1Jβ1.1Cβ2), derived from two αβ TCRs specific for the immunodominant vesicular stomatitis virus octapeptide (VSV-8) bound to the murine H-2K(b) MHC class I molecule. The crystal packing of the N15β structure reveals a homodimer formed through two Vβ domains. The Vβ/Vβ module is topologically very similar to the Vα/Vβ modul

Thymopoiesis, regulatory T cells, and TCRVbeta expression in thymoma with and without myasthenia gravis, and modulatory effects of steroid therapy.

We analyzed thymocyte and thymic regulatory T cell (CD4SPCD25+Foxp3+cells, Treg) development in thymoma with and without myasthenia gravis (MG, MG-thymoma, non-MG-thymoma) and in MG-associated non-neoplastic thymus (MG-NNT). An increased number of immature CD4+CD8(-)CD3(-) thymocytes through the CD4+CD8+ to CD4+CD8(-) transition and an abnormal T cell receptor Vbeta (TCRVbeta) development through the CD4+CD8+ to CD4(-)CD8+ transition were seen both in MG-and non-MG-thymomas. Terminal thymopoiesis, i.e., CD45RA+ cells within the CD4+CD8(-)CD3+ and CD8+CD4(-)CD3+ subsets, was skewed towards the …

Conservation of a CD1 multigene family in the guinea pig.

CD1 is a family of cell-surface molecules capable of presenting microbial lipid Ags to specific T cells. Here we describe the CD1 gene famil … least a subset of guinea pig CD1 proteins. Cell-surface expression of CD1 was detected on cortical thymocytes, dermal dendritic cells in the skin, follicular dendritic cells of lymph nodes, and in the B cell regions within the lymph nodes and spleen. CD1 proteins were also detected on a subset of PBMCs consistent with expression on circulating B cells. This …

Effects of tetracyclines on the pathologic activity of endotoxin: in vitro and in vivo studies.

Lipopolysaccharide (LPS) is considered to be one of the major virulence factors of Gram-negative bacteria. Recently, tetracyclines (TTCs) were found to prevent the patho-physiological changes associated with LPS in vivo and the secretion of inflammatory mediators in vitro. However, the mechanism by which TTCs prevents LPS-induced pathology in vivo is still unclear. In order to shed light on that problem, we carried out in vitro and in vivo experiments. TTC inhibited the secretion of nitric oxide (NO) and TNF alpha from LPS-stimulated macrophages and inhibited macrophage-induced thymocyte proli

Analysis of early reconstitution events in the SCID mouse thymus following rat bone marrow cell transplantation.

In this work, we provide comprehensive evidence that sublethally irradiated Thy-1.2 SCID mice can be used as a model system for thymus homin … ribed in congenic animals and points out the temporally distinct development of dendritic cells and thymocytes. The SCID mouse-rat chimera model system represents a new in vivo tool for manipulating rat T-cell differentiation from bone marrow-resident precursor cells and in addition supports our previous xenogeneic reconstitution studies performed in organ c …

Clonal deletion induced by either radioresistant thymic host cells or lymphohemopoietic donor cells at different stages of class I-restricted T cell ontogeny.

Major histocompatibility complex (MHC) products and self-antigens expressed in the thymus determine the repertoire of mature alpha/beta T ce … e the latter allowed positive selection but not LCMV-specific deletion of transgenic TCR-expressing thymocytes. In irradiation bone marrow chimeras expressing the restriction element for negative selection (H-2Db) on host tissue, we show that radioresistant recipient cells in the thymus deleted developing T cells at an early stage of differentiation. In cont …

A study of surface markers in non-Hodgkin's lymphoma by using anti-T and anti-B lymphocyte sera.

Cell surface markers of 44 cases of non-Hodgkin's lymphoma (NHL) were studied with various surface markers, especially by using antihuman B lymphocyte serum (ABS), antihuman thymocyte serum (ATS-T), and antihuman peripheral T lymphocyte serum (ALS-T), which were rendered specific for human B lymphocytes, human thymocytes, and human peripheral T lymphocytes, respectively. An immunofluorescent study with ABS, ATS-T, and ALS-T enabled us to demonstrate the histologic localization of normal or neoplastic B and T cells in preserving the original structure of lymphoid organs or tumor tissues. The pr…

Induced Prostanoid Synthesis Regulates the Balance between Th1- and Th2-Producing Inflammatory Cytokines in the Thymus of Diet-Restricted Mice.

Multiple external and internal factors have been reported to induce thymic involution. Involution involves dramatic reduction in size and fu … the diet-restricted thymus, without affecting the reduction of thymus size. In vitro stimulation of thymocytes with phorbol myristate acetate (PMA)/ionomycin confirmed the polarization of thymocytes from diet-restricted mice toward Th2 cells. These results indicated that the induced production of prostanoids during diet-restriction-induced thymic involution …

Loss of Bak enhances lymphocytosis but does not ameliorate thrombocytopaenia in BCL-2 transgenic mice.

Bax and Bak are critical effectors of apoptosis. Although both are widely expressed and usually functionally redundant, recent studies sugge … loss of Bak enhanced lymphocytosis in vavP-BCL-2 transgenic mice and increased resistance of their thymocytes to some cytotoxic agents, implying that Bak-specific signals can be triggered in certain lymphoid populations. Nevertheless, lack of Bak had no significant impact on thymic abnormalities in vavP-BCL-2tg mice, which kinetic analysis suggested was due …

Genetic regulation of T regulatory, CD4, and CD8 cell numbers by the arthritis severity loci Cia5a, Cia5d, and the MHC/Cia1 in the rat.

T cells have a central role in the pathogenesis of autoimmune arthritis, and several abnormalities in T cell homeostasis have been described … ained by Cia5d. DA rats also had a significantly lower frequency of CD4(+)CD25(+) and CD8(+)CD25(+) thymocytes, and of peripheral blood CD8(+)CD45RC(|o) Treg cells, compared with F344 rats, and that difference was accounted for by the MHC. This is the first identification of arthritis severity QTL regulating numbers of CD4(+)CD45RC(|o) (Cia5a) and CD8(+)CD45 …

NO-dependent regulation of lectin- and menadione-induced H2O2 production by cells from pleural effusions of lung cancer patients and by immune cells.

Molecular mechanisms of interplay between reactive oxygen (superoxide, hydroxyl radical, H2O2 etc.) and nitrogen (nitric oxide - NO, ONOO-, NO2-, NO3- etc.) forms are proposed to be of key importance for cell and tumor biology. Considering NO as a signal molecule we have studied the impact of NO release on processes of generation of H2O2 in different experimental systems including pleural effusions (PE) of lung cancer patients, human polymorphonuclear leukocytes (PMNs), and rat thymocytes. It was found that PE of lung cancer patients contain a high level of [NO2-+NO3-], i.e. 43.4 25.6 microM (…

CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system.

CD81 (TAPA-1) is a widely expressed cell-surface protein involved in an astonishing variety of biologic responses. It has been cloned indepe … timulatory signal with CD3. In fetal thymic organ culture, mAb to CD81 block maturation of CD4-CD8- thymocytes, and expression of CD81 on CHO cells endows those cells with the ability to support T cell maturation. However, CD81-deficient mice express normal numbers and subsets of T cells. These mice do exhibit diminished antibody responses to protein antigen …