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

The proportion of nucleated splenocytes bearing B-lymphocyte markers B220, surface IgM (sIgM) and sIgD, as well as the T-lymphocyte markers Thy 1.2, CD5, CD8a and CD4 were quantitated by flow cytometric analysis (FACS) throughout postpartum development in the A/J mouse. Full expression of B lymphocyte markers was achieved much sooner than expression of T lymphocyte markers. This was especially true for B220, which was found on 8% of all splenocytes at day 5 and reached adult levels (47-50%) by weaning at day 22. Expression of sIgM and sIgD were 13% and 9%, respectively, of all splenocytes at day 5 with mature levels not expressed until day 35 postpartum (approximately 36% of cells were positive for these markers). T lymphocyte markers, on the other hand, did not reach full expression until sexual maturity. For example, Thy 1.2 expression was 8% on day 5 and did not reach mature levels (28-30%) until day 56. CD5 closely paralleled Thy 1.2 expression rising from only 2% on day 5 to 27% by day 56. Likewise, CD8a and CD4 marker development paralleled one another with CD8a rising from 1% on day 5 to 10% by day 56 and CD4 rising from 5% on day 5 to 19% by day 56. These data demonstrate the variability in the time of appearance and rate of maturation of the various lymphocyte cell surface markers during postpartum development. They also serve as a reference to identify alterations in lymphocyte development created by immunodeficiency diseases.
 ...
PMID:Flow cytometric analysis of the expression of murine B and T surface markers from birth to adulthood. 134 52

Monocytes from human immunodeficiency virus (HIV) patients have an increased heterogeneity of phenotype and function. In a study of 120 HIV patients we have demonstrated that they have normal monocyte differential counts but that with progression of the disease an increasing proportion of monocytes show phenotypic and functional evidence for activation or maturation. A proportion of the monocytes are larger, with increased expression of CD11b, HLA-DR, CD45 and CD16. Concomitantly there was increased expression of TNF-alpha, high constitutive synthesis of PGE2 and high plasma IL-6 levels. This suggested that there exists a more dynamic situation of recruitment, activation and maturation of peripheral blood monocytes driven by HIV infection which results in a broader phenotypic profile.
 ...
PMID:Heterogeneity of peripheral blood monocyte populations in human immunodeficiency virus-1 seropositive patients. 146 4

In the majority of adult and pediatric patients with AIDS, hematologic abnormalities including leukopenia, anemia, and thrombocytopenia are commonly observed. In addition to these findings, changes in hematopoietic progenitor cells occur, including a reduction of multipotential-forming units, granulocyte-macrophages, macrophage as well as eosinophil colony-forming units, and bone marrow erythroid burst-forming units. This study examined alterations in human fetal liver hematopoiesis in 2nd trimester abortuses from human immunodeficiency virus (HIV)-seropositive women. The differentiation and growth potential of hematopoietic cells in vitro were monitored. Upon initial isolation, some populations of liver hematopoietic cells from abortuses of HIV-seropositive women were significantly decreased when compared to age-matched samples from fetuses of normal females including the percentage of early T cells [cluster of differentiation (CD)2], B cells (CD19), and early monocytes (CD14). A decrease in multipotent progenitors (CD34), myelomonocytes (CD33), and panleukocytes (CD45) was also observed. In contrast, after 21 d in culture, cells from HIV abortuses demonstrated an increase in the percentage of CD14 cells when stimulated with erythropoietin and granulocyte-monocyte colony-stimulating factor, as well as an increase in CD45 phenotype after exposure to granulocyte-monocyte colony-stimulating factor alone. These samples showed a persistence of erythropoietic elements (transferrin and CD36 phenotype) when compared to normal controls. No significant difference in the in vitro growth of hematopoietic progenitors (bone marrow erythroid burst-forming units, granulocyte-macrophage colony-forming units, and multipotential forming units) between these samples and normal controls was found.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Alterations in human fetal hematopoiesis are associated with maternal HIV infection. 150 4

The Wiskott-Aldrich syndrome (WAS) is a severe immunodeficiency and platelet deficiency disease arising from an X-linked defect. The disease is correctable by transplantation of hematopoietic stem cells, but the product of the defective gene is unidentified and the number of defects in patient blood cells is large. The current hurdle is the need to identify the early pathogenic event(s) that are the cause of other defects. As a step toward this goal, we have generated and examined a panel of interleukin 2-dependent allospecific T cell lines from peripheral lymphocytes of seven WAS patients and five normal individuals. WAS cell lines, like normal lines, undergo vigorous proliferation when challenged with specific allostimulant or with phorbol myristate acetate and ionomycin. Both normal and WAS T cell lines express cell surface molecules CD2, CD3, T cell receptor-alpha/beta, human histocompatibility leukocyte antigen class I, CD45 and CD11a, and varying ratios of CD4 and CD8, and are negative for natural killer cell and monocyte surface molecules. WAS T cell lines express CD43 (sialophorin/leukosialin) with molecular weight and in an amount comparable with normal T cell lines. WAS T cell lines thus do not express defects in CD43 (decreased amount, abnormal molecular weight), previously documented in WAS circulating lymphocytes. On the other hand, as detected by scanning electron microscopy, WAS cell lines exhibit severe morphological abnormalities, including decreased size and density of the microvillus surface projections. The morphological abnormalities of WAS T cell lines are similar to, or more extensive than, those previously reported for WAS peripheral lymphocytes, indicating that the generation of morphological (cytoarchitectural) defects is an early pathogenic event in this disease. The findings suggest that the gene that is defective in the WAS encodes a protein that normally functions to maintain or regulate the cytoskeletal structure of blood cells.
 ...
PMID:T cell lines characterize events in the pathogenesis of the Wiskott-Aldrich syndrome. 151 49

A human CD4+ T cell line, Jurkat, was transfected with a constructed plasmid, which has the envelope gene of the human immunodeficiency virus (HIV) under the transcriptional control of the human metallothionein IIA promoter, and these transfected cells were then cloned. JME2, one of the cloned cell lines, expressing the envelope glycoprotein after induction with metal ions, showed the ability to form syncytia involving other CD4+ cells not expressing the HIV envelope protein. When several CD4+ cell lines were examined for their susceptibility to syncytium formation by JME2 cells, the p56lck-expressing cell lines were found to be more susceptible to syncytium formation than the p56lck-non-expressing cell lines. To substantiate the role of p56lck in the syncytium formation, a CD4+, p56lck-non-expressing monocytoid cell line, U937 clone 2, was transfected with an lck-expressing construct. Using such transfectant cell clones, it was demonstrated that p56lck-positive cells are markedly more susceptible to the syncytium formation than p56lck-negative cells, implying a regulatory role for p56lck in syncytium formation mediated by the HIV envelope and CD4 molecule. Moreover, it was suggested, in the experiments using CD45 cross-linking or a protein tyrosine kinase inhibitor, genistein, that p56lck affects syncytium formation through its protein tyrosine kinase activity. A putative mechanism by which p56lck affects the syncytium formation is also discussed.
 ...
PMID:The effect of p56lck, a lymphocyte specific protein tyrosine kinase, on the syncytium formation induced by human immunodeficiency virus envelope glycoprotein. 162 97

Plasmacytoma-bearing mice (PC-mice) develop a polyclonal B cell immunodeficiency syndrome characterized by marked impairment of: a) primary antibody responses and b) proliferative responses to B cell mitogens. The present investigations used two-color flow cytometry to examine B lymphocytes from the spleens and lymph nodes of PC-mice and found decreased surface membrane expression of surface IgM (sIgM), transferrin receptors (TfR) and IgE FcR (CD23), increased expression of class II MHC, but normal expression of B220, Mel-14, Fc gamma RII, and Fc mu R. These changes were not related to the H chain class or the amount of Ig produced by the plasmacytoma. When cultured with IL-4, B lymphocytes from PC-mice increased their expression of sIgM and class II MHC, but not of CD23. Several findings implicate transforming growth factor-beta 1 (TGF-beta 1) in the mechanism that modulates receptor expression on B lymphocytes in PC-mice: a) ascites fluid from PC-mice contains large quantities of TGF-beta 1; b) supernatants of cultured spleen cells from PC mice contain up to eightfold more TGF-beta than is found with normal spleen cells; c) cloned plasmacytoma cells produce TGF-beta in vitro; and d) the abnormal phenotype of B cells from PC-mice, i.e., decreased CD23, sIgM, and TfR, and increased class II MHC, is induced on normal B cells cultured in the presence of TGF-beta 1. Because sIgM, TfR, class II MHC, and CD23 are molecules that play fundamental roles in the activation of normal B cells, their modulation by TGF-beta 1: a) identifies molecular mechanisms that could account for some of the known immunosuppressive properties of TGF-beta 1 and b) implicates TGF-beta in the pathogenesis of the polyclonal B cell immunodeficiency that is characteristic of plasma cell tumors.
 ...
PMID:Immune dysfunction in mice with plasmacytomas. I. Evidence that transforming growth factor-beta contributes to the altered expression of activation receptors on host B lymphocytes. 182 99

The differential expression of various membrane CD45R isoforms by normal lymphocyte populations is known to be closely associated with distinct immunoregulatory functions. Abnormal patterns of CD45R expression have been reported in patients with common variable immunodeficiency and HIV infection, and recent evidence has suggested the possibility that one type of variant CD45R expression may be inheritable. By multiple colour flow cytometry, we studied the immunological characteristics of CD4+ helper/inducer and CD8+ suppressor/cytotoxic T cells in a family with variant CD45R expression over three generations. This variant pattern of CD45R expression was shown to affect both CD4+ and CD8+ lymphocyte populations in individual family members and was immunologically characterized by a failure of the normal reciprocal expression of the CD45RA and CD45RO isoforms. Family studies also revealed that this trait had an autosomal dominant mode of inheritance and, in the heterozygous state, appeared not to be associated with major clinical abnormalities. The different isoforms of CD45 show distinct patterns of expression during lymphocyte ontogeny and activation, and these patterns appear to closely reflect function. Despite their diverse immunological roles, our finding that both CD4+ and CD8+ T cells in affected family members showed the same defect suggests a common regulatory mechanism(s) for both these lymphocyte populations. The recognition of this abnormality, particularly in homozygous individuals, will be of great importance in understanding the role of these molecules in immune function and disease.
 ...
PMID:Variant CD45R expression with autosomal dominant inheritance affects both helper/inducer (CD4+) and suppressor/cytotoxic (CD8+) T cell populations. 183 61

The effects of systemic graft-versus-host (GVH) reactions on the early precursor cell populations involved in primary B lymphocyte genesis have been examined in the bone marrow of (C57BL/6xA)F1 mice injected with lymphoid cells from A strain mice. Double immunofluorescence labeling techniques for the intranuclear enzyme, terminal deoxynucleotidyl transferase (TdT), the B220 cell surface glycoprotein detected by monoclonal antibody, 14.8, and surface or cytoplasmic mu chains of IgM (s mu, c mu) were used to quantitate 3 putative early B lineage progenitors preceding mu chain expression (TdT+14.8-mu-, TdT+14.8+mu- and TdT-14.8+mu-), pre-B cells (c mu+, s mu-) and B lymphocytes (s mu+). After initiating GVH reactions, the early B precursor cells, pre-B cells, and B lymphocytes in the bone marrow all fell rapidly in numbers, being almost completely absent from 10-15 days to the end of the 30-day assay period. The decline of some of the early progenitors started at a later time and was less complete than that of the more differentiated B lineage cells. In the spleen, B lymphocytes declined rapidly in numbers after 8 days to less than 5% of normal values from 12 days onward. The results demonstrate that systemic GVH reactions in mice almost completely eliminate the B cell lineage, including early precursor cells apparently undergoing mu chain rearrangement in the bone marrow. The pattern of depletion suggests that a range of B lineage progenitor cells may be directly susceptible to GVH reactions. The findings contribute to a model for the pathogenesis of the humoral immunodeficiency of systemic GVH disease.
 ...
PMID:The effect of the graft-versus-host reaction on B lymphocyte production in bone marrow of mice. Depressed genesis of early progenitors prior to mu heavy chain expression. 190 23

Previous studies have shown that the injection of parental T cells into MHC class II mismatched F1 recipient mice can lead to graft-vs-host (GvH) reaction that manifests itself by multiple symptoms. The objective of our study was to analyze GvH reactivity induced by a single T cell clone specific for host I-A or I-E alloantigen. The T cell clones tested for GvH potential were CD4+, with or without cytolytic activity in vitro and with a lymphokine pattern that classifies them as Th1 cells. The inoculation of a single T cell clone induced a severe, but transient immunodeficiency in the host that was independent of its cytolytic activity, as demonstrated by the failure to generate a CTL response to third party allogeneic cells in vitro. Induction of immunodeficiency in the recipients required preactivation of the clones in vitro by rIl-2 and the presence of the stimulator class II alloantigen in the host. Spleen cells from these mice lacked suppressor cells, they were deficient in Il-2 secretion and exhibited a decrease in the number of CD4+ T cells. In addition, I-E expression was reduced, however, without any changes in the macrophage population and an increase in surface Ig and the B cell marker B220. Simultaneous to the immunodeficiency, the clone-injected mice produced elevated antibody titers to ssDNA.
 ...
PMID:Induction of graft versus host-associated immunodeficiency by CD4+ T cell clones. 197 25

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.
 ...
PMID:X-linked lymphoreticular disease in the scurfy (sf) mutant mouse. 205 95


1 2 3 4 5 6 7 8 9 10 Next >>