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)

Human and mouse cell lines that expressed a CD4/Thy-1 fusion protein on the cell surface were constructed and tested for the capacity to be infected with human immunodeficiency virus. The human cell lines, in contrast to the mouse line, were infectable. The CD4/Thy-1 fusion, which is anchored to the membrane by a glycosylphosphatidylinositol tail rather than a peptide linkage, can therefore serve as a human immunodeficiency virus receptor. In addition, this molecule, like CD4, is down-modulated in its cell surface expression by exogenous gangliosides.
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PMID:Glycosylphosphatidylinositol-anchored CD4/Thy-1 chimeric molecules serve as human immunodeficiency virus receptors in human, but not mouse, cells and are modulated by gangliosides. 167 Jun 44

Some strains of mice inoculated with LP-BM5 murine leukemia virus (MuLV) develop a syndrome, termed mouse acquired immunodeficiency syndrome (MAIDS), characterized by progressive lymphoproliferation and profound immunodeficiency. LP-BM5 MuLV is a virus mixture that contains ecotropic (eco) and mink cell focus-induced MuLV and a defective genome that is the proximal cause of disease. Flow cytometry analyses of spleen and lymph nodes from susceptible C57BL/6 mice infected with this virus mixture revealed the presence in spleen and peripheral lymph nodes of a previously unrecognized subset of CD4+CD3+ T cells that are Thy-1-. The frequency of these cells increased with progression of disease, eventually comprising between 30% and 50% of all CD4+ cells. Infection of A/J mice, a strain which is genetically resistant to development of MAIDS, did not induce an increase of this T cell population, indicating that infection with the virus mixture was insufficient to induce its proliferation. A central role for the defective virus in this process was suggested by the finding that C57BL/6 mice infected with LP-BM5 eco alone did not have increased frequencies of Thy-1-CD4+ cells in spleen. Studies of spleen and peripheral lymph node cells from normal mice demonstrated the presence of Thy-1-CD4+ cells at frequencies of 1%-2%. Studies using two anti-T cell monoclonal antibodies, SM6C10 and SM3G11, that define four CD4+ subsets showed that Thy-1-CD4+ T cells from normal and infected mice were present only in the 6C10- subsets.
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PMID:A unique subset of normal murine CD4+ T cells lacking Thy-1 is expanded in a murine retrovirus-induced immunodeficiency syndrome, MAIDS. 198 Jan 14

Scurfy (sf) is a spontaneous, sex-linked, recessive mutation that maps to the extreme proximal portion of the X chromosome, about 2 centimorgans from sparse fur (spf). Hemizygotes for sf manifest several clinical disorders, evident at 14 days of age, including scaliness and crusting of the eyelids, ears, and tail, runting, reddening and swelling of the genital papilla, anemia, cachexia, and early death (average, 24 days). Our studies indicate that the phenotype of hemizygous scurfy is not, as has been suggested, a model for human X-linked ichthyosis, but appears to be a disease primarily affecting the lymphoreticular, and possibly the hematopoietic, systems. Gross lesions include marked splenomegaly, hepatomegaly, enlarged lymph nodes, and variable thickening of the ears. The characteristic histologic lesion is a lymphohistiocytic proliferation and infiltration of peripheral lymph nodes, spleen, liver, and skin. In routine hematoxylin and eosin-stained sections, these lesions efface lymph node architecture, thicken the dermis, and form nodular portal infiltrates in the liver. Scurfy lesions characteristically contain a population of large blastlike cells with round to oval nuclei, a vesicular chromatin pattern, and prominent single nucleoli. Mixed perivascular infiltrates of lymphocytes, macrophages, and granulocytes sometimes are found in kidney, heart, pancreas, lung, and mesenteries. There is excessive hematopoiesis in the liver and spleen. Cells expressing B220 or Thy-1 antigens localize to appropriate areas in the lymph nodes and spleen, but are rare in the portal infiltrates and are absent from the skin. There is a marked, polyclonal increase in serum IgG, severe Coombs'-positive anemia, and leukocytosis with atypical mononuclear cells. Scurfy mice are negative for antinuclear antibodies. Despite their morphologically aberrant lymphoreticular system, scurfy mice can exist in a conventional environment without evidence of opportunistic infection. Raising scurfy mice in a specific-pathogen-free environment does not alter disease expression. Thus, while our findings indicate that scurfy disease may be the result of immune dysfunction, it is not a classic immunodeficiency.
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PMID:X-linked lymphoreticular disease in the scurfy (sf) mutant mouse. 205 95

Ataxia telangiectasia (A-T) is an autosomal recessive disorder characterised by progressive neurological degeneration, oculocutaneous telangiectasia, immunodeficiency and a high incidence of lymphoid tumours. A prerequisite to gaining a complete understanding of the basic defect that results in these features is the localization of the gene(s) involved. We report here a linkage analysis using seven polymorphic markers, which map to 11q22-23, on a sample of 35 consecutively obtained families from the British Isles showing this disorder. In a pairwise analysis, the strongest support for linkage was a lod score of 4.01 at zero recombination from Thy-1. This result supports a previous report showing linkage of the A-T gene to 11q22-23. We have also obtained evidence in a multipoint analysis for a more centromeric A-T-linked locus in the region between YNB 3.12/CJ52.208 and 2-7-1D6. This observation is also supported by inspection of the haplotypes of selected recombinants.
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PMID:Analysis of 7 polymorphic markers at chromosome 11q22-23 in 35 ataxia telangiectasia families; further evidence of linkage. 237 52

Infection by the human immunodeficiency virus (HIV) induces T cell immunity in humans, chimpanzees and macaques. The protective value of this immune response is not clear. We have consequently developed a murine experimental system to study HIV-specific CD4 and CD8 T lymphocyte immunity in vitro and in vivo. BALB/c, DBA/2 and C3H/He mice were immunized with vaccinia virus (VV) recombinant VV-11.39 which expresses the gp160 glycoprotein of HIV-1. Primary and secondary cytotoxic T lymphocyte response to HIV were detected with histocompatible mouse target cells transfected with the HIV-1 env gene. Killer cells were positive for the Thy-1 and Ly-2 (CD8) T cell markers, and were restricted by class I H-2 histocompatibility antigens. Immunological memory specific for HIV-1 envelope antigens was clearly induced by vaccination with VV-11.39:spleen cells from mice vaccinated 4 weeks or more prior to assay generated CD4 and CD8 T lymphocyte responses following stimulation in vitro with HIV envelope antigens. The intensity of these responses increased with consecutive vaccinations, indicating that HIV-specific precursor T cell pools were progressively amplified. Finally, DBA/2 mice vaccinated with VV-11.39 developed protective immunity against a syngeneic tumor which expresses HIV-1 env antigens, leading to accelerated tumor rejection and increased survival.
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PMID:HIV-specific T lymphocyte immunity in mice immunized with a recombinant vaccinia virus. 290 93

Irradiated CBA/J mice transplanted with H-2 compatible, minor histocompatibility disparate B10.BR bone marrow develop graft-versus-host disease (GVHD) if mature T lymphocytes are added to the marrow inoculum. In the setting of mild GVHD (receiving 10(4) or 10(5) T cells), by phenotypic analysis, lymphoid reconstitution occurs normally within 4 to 6 wk but there is a profound deficiency in the ability of splenic lymphocytes to respond to polyclonal activators such as LPS and Con A. This unresponsiveness is attributable to active suppression mediated by cells that express Thy-1 and can be removed with leucine methyl ester treatment. Thus, splenocytes from mice with GVHD suppress responses of normal T and B lymphocytes. Moreover, depletion of these suppressor cells restores normal function to splenocytes from mice with GVHD, and B cells isolated from these mice respond normally to T-dependent and -independent stimulation. Finally, IFN-gamma plays an important role in this suppression, because a neutralizing anti-IFN-gamma mAb significantly removes suppression of normal cells and restores functional responses of lymphocytes from mice with GVHD. These results provide insights into the mechanisms of immunodeficiency associated with GVHD, and suggest novel strategies for possible therapies for this disorder.
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PMID:Immunodeficiency in graft-versus-host disease. I. Mechanism of immune suppression. 312 5

Aged NZB/NZW F1 hybrid (B/W) mice spontaneously develop severe immunodeficiency disease associated with worsening autoimmunity and malignancies of the immune system. The impaired immune response is mediated in part by markedly increased suppressor cell activity in the spleens of these animals. In male B/W mice, the suppressor cell is nonphagocytic, nonadherent to nylon wool columns and highly resistant to treatment with anti-Thy-1 + complement. We report here marked ablation of splenic suppressor activity by anti-Lyt-1.2 + complement and to a much smaller extent by anti-Ly-2.2. The suppressor activity is not affected by anti-IgM + complement. These data suggest that the suppressor cell activity in the spleens of aged male B/W mice are in the T cell line and may result from an underlying disorder of T cell maturation and differentiation.
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PMID:Surface markers of suppressor cells in the spontaneous immunodeficiency disease of senescent NZB/NZW F1 hybrid mice. 315 98

Studies were performed to determine whether pre-T cells develop normally in the bone marrow of mice displaying thymic dysplasia and T cell immunodeficiency as a consequence of a graft-versus-host (GVH) reaction. GVH reactions were induced in CBAxAF1 mice by the injection of A strain lymphoid cells. To test for the presence of pre-T cells in GVH-reactive mice, bone marrow from GVH-reactive mice (GVHBM) was injected into irradiated syngeneic F1 mice and 30-40 days later thymic morphology and function were studied. Morphology studies showed nearly normal thymic architectural restoration; moreover, such glands contained normal numbers of Thy-1-positive cells. Functional pre-T cells were evaluated by transferring thymocytes from the irradiated GVHBM-reconstituted mice into T-cell-deprived mice. These thymocytes reconstituted allograft reactivity, T helper cell function and Con A and PHA mitogen responses of T-cell-deprived mice. These results suggest that the pre-T cell population in the bone marrow is not affected by the GVH reaction. Therefore, the T cell immunodeficiency associated with the GVH reaction is not due to a deficiency of pre-T cells in the bone marrow but is more likely associated with GVH-induced thymic dysplasia.
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PMID:The graft-versus-host reaction and immune function. III. Functional pre-T cells in the bone marrow of graft-versus-host-reactive mice displaying T cell immunodeficiency. 348 49

Motheaten mice develop combined immunodeficiency and fatal autoimmune disease that follow autosomal recessive inheritance. In splenocyte cultures of motheaten mice, supplemented with 5% normal serum proliferating cells (MP) were present exhibiting morphologic characteristics of mononuclear phagocytes at light and electron microscopic levels. The macrophage nature of these cells was confirmed by the lack of Thy-1 antigen and immunoglobulins; the expression of Mac-1 antigen, FcR for IgG, and Ia antigens on their cell surfaces; their ability to phagocytize EA and adhere to plastic; the presence of nonspecific esterase and lysomal enzymes in their cytoplasm; and the pattern of peroxidase localization similar to monocyte-derived macrophages. MP from motheaten mice exponentially grew in culture in the absence of exogenous growth factors with a doubling time of approximately 76 hr. Although these cells were present in splenocyte cultures of normal controls, their number did not increase during the culture period under the same conditions. The addition of dextran sulfate further enhanced the proliferation of MP from motheaten mice, and induced exponential growth of these cells from normal controls, reaching only the level of unstimulated cells from motheaten mice. Radioautographic analysis demonstrated that MP substantially contributed to the elevated spontaneous and dextran sulfate-induced DNA synthesis in splenocyte cultures. Therefore, the in vitro abnormality of MP may be indicative of in vivo aberrancies of macrophages from motheaten mice and lends credence for investigating the role of macrophages in immunodeficiency and autoimmunity that develop very early in motheaten mice.
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PMID:Abnormal in vitro proliferation of splenic mononuclear phagocytes from autoimmune motheaten mice. 617 15

Thymic epithelium from three patients with severe cellular immunodeficiency diseases were compared with age-matched normal thymic epithelium using three markers of human thymic epithelium and antibodies against thymosin alpha 1, thymopoietin, and thymosin beta 4. We have previously shown that normal thymic epithelium reacts with antibodies against GQ gangliosides (antibody A2B5) and binds tetanus toxin (TT). In addition, some areas of normal thymic epithelium express human Thy-1 antigen. We found thymic epithelium in patients with severe cellular immunodeficiency diseases to be different from normal subjects. Two children with severe combined immunodeficiency disease (SCID) had thymic epithelium that bound anti-GQ ganglioside antibody but, unlike in normals, did not bind TT. The patient with severe cellular immunodeficiency and normal serum immunoglobulins (Nezelof syndrome) had thymic epithelium that bound TT but, unlike normal thymic epithelium, did not react with anti-GQ ganglioside antibody. Thymic epithelium from both SCID and Nezelof syndrome patients contained thymosin alpha 1, thymopoietin, and thymosin beta 4 and expressed human Thy-1 antigen. In contrast to SCID thymus rudiments, Nezelof thymus contained numerous (though fewer than normal) lymphocytes with mature T cell surface antigens. Thus, using these probes of human thymic epithelium, we have demonstrated heterogeneous defects in thymic epithelial surface marker expression in severe primary cellular immunodeficiency diseases. These defects presumably reflect abnormalities of in vivo thymic epithelial maturation.
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PMID:Demonstration of abnormalities in expression of thymic epithelial surface antigens in severe cellular immunodeficiency diseases. 660 Apr 76


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