Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An in vivo murine model for immunodeficiency of both B and T cells is produced by continuous intraperitoneal infusion of 2'-deoxycoformycin (DCF), a specific tightly binding inhibitor of adenosine deaminase (ADase; adenosine aminohydrolase, EC 3.5.4.4). After DCF infusion, ADase of thymus, spleen, and lymph nodes was inhibited to varying degrees ranging from 57% to 100%. Immunodeficiency under these conditions was indicated by: (i) a striking decrease in lymphocyte response to the T-cell mitogens concanavalin A and phytohemagglutinin; (ii) an impairment of delayed hypersensitivity measured by the footpad reaction; (iii) a decrease in antibody production measured in both in vivo and in vitro plaque-forming cell assay; (iv) a significant prolongation of mouse skin allograft survival after transplantation into the C57BL/6J (H-2b) strain of skin from BALB/c (H-2d) mice; and (v) a marked lymphopenia. Histological examination indicated lymphoid degeneration in the thymus, lymph nodes, and spleen with no alterations in other tissues including bone marrow, kidney, lung, gastrointestinal tract, and liver except for the occurrence of hepatitis. A decrease in the number of Thy-1-positive cells in both spleen and lymph nodes further supported the fact of cytotoxicity of DCF to T cells. Anorexia and weight loss were observed within 5 days of continuous DCF infusion at 0.4 mg/kg body weight per day. These data indicate that this method provides an experimental model for future studies on the biochemical mechanisms responsible for the genetically determined severe combined immunodeficiency disease in man.
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PMID:Animal model for immune dysfunction associated with adenosine deaminase deficiency. 696 8

AKR mice were protected from lethal irradiation and established as long-lived chimeras by transplanting allogeneic C57BL/6 (B6) bone marrow that had been treated in vitro with anti-Thy-1 antiserum without complement. In these chimeras, which were designated [B6 {arrow} AKR], virtually all the thymus and spleen cells were shown to be derived from the B6 donor; several immune functions studied in these chimeras were as follows: (a) The chimeric mice were tolerant of histocompatibility antigens of both donor and recipient strain and nearly fully reactive to antigens of third party, as revealed by Simonsen's splenomegaly assay. The tolerance of these chimeras could not be attributed to suppressor cells but was compatible with clonal depletion. (b) Proliferative responses to concanavalin A, phytohemagglutinin, and lipopolysaccharide as well as natural killer and antibody-dependent cell- mediated cytotoxicity activity of the chimeric mice was normal. (c) Plaque- forming cell (PFC) assays of antibody responses to sheep erythrocytes (SRBC) showed gross deficiency in the primary response of the [B6 {arrow} AKR] and [AKR {arrow} B6] chimeras. By contrast, [B6-H-2(k)(E(k)) {arrow} AKR] H-2-compatible chimeras and [AKR {arrow} AKR] syngeneic marrow transplanted mice had normal primary PFC responses. PFC responses after secondary stimulation with SRBC, however, revealed vigorous direct plaque formation and substantial but somewhat smaller indirect plaque formation in the [B6 {arrow} AKR] chimeras. This observation favors operationally the concept of adaptive differentiation proposed by Katz et al. (44). (d) Analysis of ability of the chimeras to develop and express delayed-type hypersensitivity responses to contact sensitizer (2,4-dinitro-l-fluorobenzene [DNFB]) showed no apparent immunodeficiency of either chimeras to this form of immunization. Development of immunologic tolerance to DNFB, however, was grossly deficient in [B6 {arrow} AKR] chimeras but normal in [AKR {arrow} AKR], [B6 {arrow} B6], and [E(k) {arrow} AKR] chimeras. These findings indicate that full chimeras across major histocompatibility complex have considerable immunologic vigor even though primary immune responses that require histocompatibility between interacting cell types are initially defective.
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PMID:Humoral and cell-mediated immune responses in fully allogeneic bone marrow chimera in mice. 698 46

Increased numbers of CD4+ Thy-1- cells have been described in the spleen (SP) of mice with retrovirus-induced immunodeficiency (MAIDS). Since this phenotypic abnormality might have considerable functional importance, the expansion of the CD4+ Thy-1- subset in MAIDS was characterized further. CD4+ Thy-1- and Thy-1+ T-cells from infected mice expressed similar densities of CD3 and TCR alpha/beta. In contrast, the Thy-1- subset was uniformly CD44hi, even early in the disease when part of Thy-1+ cells were still CD44lo. The emergence of CD4+ Thy-1- cells occurred first in SP and lymph nodes and was observed later in thymus. The important fraction of CD4+ cells lacking Thy-1 normally present in Peyer's patches was only weakly modified. Despite the major expansion of the CD4+ Thy-1- phenotype, the proliferating fraction was not higher in this subset than in CD4+ Thy-1+ cells from infected mice. Persistence after hydroxyurea administration was identical in both subsets, indicating similar mean cell lifespans. Taken together, these results show that the major expansion of CD4+ Thy-1- T-cells in MAIDS is not ascribable solely to increased proliferation within this subset. Phenotypic analysis suggests that CD4+ Thy-1- cells result from the differentiation of Thy-1+ cells induced by activation signals related to retroviral infection.
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PMID:Population dynamics of CD4+ T cells lacking Thy-1 in murine retrovirus-induced immunodeficiency syndrome (MAIDS). 750 99

Due to self-renewal of the peripheral pool of T-cells, adult thymectomy has normally little influence on immunocompetence. However, thymus might play a more important role in the setting of viral-induced cytopathic effects on T-cells in the periphery. Therefore, thymus weight, cell numbers, and subset distribution were sequentially analysed after infection with RadLV-Rs, a viral mixture known to induce murine retrovirus induced immunodeficiency (MAIDS). Infection induced thymic atrophy (concerning organ weight as well as total cell number) which culminated seven weeks after inoculation. The atrophic process mostly reflected the depletion of double positive CD4+ CD8+ cells since their proportion sharply decreased around week 6. Single positive T-cells were less affected by the process. The proportion of B-cells progressively increased. Surprisingly, there was a strong correlation between the extent of atrophy and the frequency of B-cells in the thymus. Finally, an abnormal CD4+ T-cell subset lacking Thy-1 and previously described in the periphery also appeared in the thymus and its frequency was strongly correlated with the expansion of B-cells in this organ.
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PMID:Thymus involvement in murine acquired immunodeficiency (MAIDS). 753 29

We describe a novel reporter molecule, the murine surface antigen Thy-1, useful for immunoselection and detection of retrovirus-mediated transduction by flow cytometry. A cDNA encoding the murine thy-1 gene was isolated, and cell surface expression of its gene product was demonstrated. The Thy-1 glycoprotein was tested as a cell surface reporter molecule in the context of replication-defective and -competent retroviruses. Cells transduced via murine retroviral vectors carrying the thy-1 and the neomycin phosphotransferase genes express Thy-1 glycoprotein on their surfaces. The Thy-1 marker is potentially useful in gene transfer protocols because selection of transduced cells can be achieved by immunoselection with anti-Thy-1 antibodies shortly after infection with the retroviral vector. In addition, a human immunodeficiency virus type 1 (HIV-1) recombinant expressing Thy-1 is described, which is replication-competent and syncytium-inducing in human peripheral blood mononuclear cells (PBMCs) and immortalized CD4-positive cell lines. Cells infected with this HIV-1 recombinant express Thy-1 on their surfaces and can be detected and purified by fluorescence-activated cell sorting (FACS). Because of these properties, retroviruses expressing this genetic marker can be useful for studies in gene therapy and of the retroviral life-cycle.
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PMID:A new reporter system for detection of retroviral infection. 758 11

We have previously reported a new spontaneous recessive mutation that induces a generalized lack of lymph nodes (LNs) and Peyer's patches (PPs) accompanied by immunodeficiency in mice (gene symbol, aly). In this study, we have analyzed gut-associated lymphatic tissues of the mutant aly/aly mice and have compared the intestinal intraepithelial T lymphocytes (IEL) in aly/aly and normal aly/+ littermate mice. Immunohistochemical studies revealed that colonization of IEL and lamina propria T cells takes place in the absence of PPs and IgA-producing B cells in the lamina propria. Absolute numbers of Thy-1- IEL-alpha beta and -gamma delta are not altered in aly/aly mutant mice, whereas absolute numbers of Thy-1+ IEL-alpha beta and -gamma delta in aly/aly mice are about half of those in aly/+ mice. In IEL-alpha beta from aly/aly mice, the major CD8 alpha alpha+ and CD8 alpha beta+ subsets are maintained, whereas CD4+ and CD4+, CD8+ subsets are reduced. Although the population size of major CD8 alpha alpha+ and CD4-, CD8- IEL-gamma delta subsets is slightly reduced, the use of TCR-gamma- and -delta-chain variable gene segments by IEL-gamma delta remains almost the same in aly/aly mice. The constitutive cytolytic activity of IEL-alpha beta and -gamma delta is attenuated sharply in the aly/aly condition. This activity is, however, augmented significantly after in vitro stimulation with anti-CD3 mAb. These results indicate that most of the IEL subpopulations develop independently of passage through PPs and mesenteric LNs and that the aly mutation interrupts cytotoxic IEL development during relatively late differentiation steps that convert cytotoxic precursors to the constitutively cytolytic state.
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PMID:Development of intestinal intraepithelial T lymphocytes is independent of Peyer's patches and lymph nodes in aly mutant mice. 805 6

Four chimeric human immunodeficiency virus type 1 (HIV-1) env genes were constructed which encoded the extracellular domain of either the wild-type or a cleavage-defective HIV-1 envelope glycoprotein (gp160) fused at one of two different positions in env to a C-terminal glycosyl-phosphatidylinositol (GPI) attachment signal from the mouse Thy-1.1 glycoprotein. All four of the constructs encoded glycoproteins that were efficiently expressed when Rev was supplied in trans, and the two cleavable forms were processed normally to gp120 and a chimeric "gp41." The chimeric glycoproteins, in contrast to the wild-type glycoprotein, could be cleaved from the surface of transfected cells by treatment with phosphatidylinositol-specific phospholipase C, indicating that they were anchored in the plasma membrane by a GPI moiety. These GPI-anchored glycoproteins were transported intracellularly at a rate only slightly lower than that of the full-length HIV-1 glycoprotein and were present on the cell surface in equivalent amounts. Nevertheless, all four glycoproteins were defective in mediating both cell-cell and virus-cell fusion as determined by syncytium formation in COS-1-HeLa-T4 cell mixtures and trans complementation of an env-defective HIV-1 genome.
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PMID:Expression and characterization of glycophospholipid-anchored human immunodeficiency virus type 1 envelope glycoproteins. 810 10

Infection of susceptible strains of mice with the Duplan strain of murine leukemia viruses induces a syndrome called MAIDS (murine acquired immunodeficiency syndrome) characterized by immunodeficiency and lymphoproliferation. In addition to a complete refractoriness of most subsets of lymphocytes to mitogen stimulation, the development of phenotypic abnormalities occurs such as the appearance of an abnormal CD4+ T cell subset lacking membranes Thy-1. This study was performed to compare the calcium responses during the early stages of MAIDS (week 9 or earlier) between T cells and B cells and between CD4+Thy-1- and CD4+Thy-1+ T cells. B cells were strikingly less affected than T cells: their baseline [Ca2+]i did not significantly increase, and their calcium response to anti-IgM antibody and concanavalin A (Con A) was partially maintained. In contrast, the response to Con A was completely abolished in T cells. Interestingly, calcium mobilization in response to membrane receptor-independent stimuli such as ionophores and thapsigargin was strongly inhibited in T cells, while no such inhibition was found in B cells. In comparison with their CD4+Thy-1+ counterparts, CD4+Thy-1- T cells had blunted calcium responses in controls, as well as in infected mice. However, CD4+Thy-1+ T cells were also strikingly altered, suggesting that the loss of membrane Thy-1 could be associated with, but not directly responsible for abnormalities of calcium responses in CD4+ T cells from RadLV-Rs-infected mice.
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PMID:Subset-specific analysis of calcium fluxes in murine AIDS. 894 66

RadLV-Rs infection induces a murine immunodeficiency syndrome associated with a dramatic enlargement of spleen and lymph nodes. Surprisingly, the lymphoproliferation excludes thymus and Peyer's patches (PP). To understand the cellular interactions underlying lymphoproliferation further, the authors investigated the fate of PP in RadLV-Rs infected mice. The atrophy of PP was mostly due to the depletion of B cells, while the proportion of CD4+ and CD8+ T cells was increased. Nevertheless, B cell phenotype was modified with the emergence of lymphocytes with a low expression of B220 in infected PP. T cells characterized by a memory/activated phenotype in control PP did not undergo phenotypical changes after viral infection (i.e. regarding Thy-1 and CD44 expression). Despite the absence of lymphoproliferation, PP T and B cells displayed altered responses to mitogens in vitro. Finally, alterations of the expression of adhesion molecules and vascular addressins could not explain the atrophy of PP by a reduced homing to this lymphoid site. B cells and T cells from normal PP are clearly different from lymph nodes (LN) lymphocytes. The authors propose that the particular functional state which characterizes PP lymphocytes influences the B cell/T cell crosstalk necessary for RadLV-Rs-induced lymphoproliferation.
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PMID:Peyer's patches in murine AIDS: dissociation between lymphoproliferation and anergy. 904 30

The objective of this study was to determine the effects of primary simian immunodeficiency virus (SIV) infection on the prevalence and phenotype of progenitor cells present in the gastrointestinal epithelia of SIV-infected rhesus macaques, a primate model for human immunodeficiency virus pathogenesis. The gastrointestinal epithelium was residence to progenitor cells expressing CD34 antigen, a subset of which also coexpressed Thy-1 and c-kit receptors, suggesting that the CD34(+) population in the intestine comprised a subpopulation of primitive precursors. Following experimental SIVmac251 infection, an early increase in the proportions of CD34(+) Thy-1(+) and CD34(+) c-kit+ progenitor cells was observed in the gastrointestinal epithelium. In contrast, the proportion of CD34(+) cells in the thymus declined during primary SIV infection, which was characterized by a decrease in the frequency of CD34(+) Thy-1(+) progenitor cells. A severe depletion in the frequency of CD4-committed CD34(+) progenitors was observed in the gastrointestinal epithelium 2 weeks after SIV infection which persisted even 4 weeks after infection. A coincident increase in the frequency of CD8- committed CD34(+) progenitor cells was observed during primary SIV infection. These results indicate that in contrast to the primary lymphoid organs such as the thymus, the gastrointestinal epithelium may be an early extrathymic site for the increased prevalence of both primitive and committed CD34(+) progenitor cells. The gastrointestinal epithelium may potentially play an important role in maintaining T-cell homeostasis in the intestinal mucosa during primary SIV infection.
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PMID:Gastrointestinal epithelium is an early extrathymic site for increased prevalence of CD34(+) progenitor cells in contrast to the thymus during primary simian immunodeficiency virus infection. 1019 59


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