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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have demonstrated the utility of measuring subsets of CD8+ T cells as prognostic markers in epidemiology cohort studies of human immunodeficiency virus (HIV)-infected patients. Most of these studies evaluating the value of CD8+ T-cell subsets have been performed at single centers, and few data are available on variability in the measurement of the CD8+ cell populations in multicenter trials. In the current study, we addressed this question by evaluating interlaboratory variability from the five laboratories enrolled in the Women and Infants Transmission Study sponsored by the National Institutes of Health. This study evaluated 35 HIV-positive and 28 HIV-negative proficiency testing samples sent to the laboratories for evaluation. The study focused on the robust coefficient of variation (RCV) for CD38 (11%), HLA-DR (21%), and CD57 (15%) expression on the CD8+ population. Data from the current study indicated that the variability in these measurements is greater than that for CD3+ CD4+ (RCV, 5%) and CD3+ CD8+ (RCV, 5%) cells. Knowledge of the variability of the CD8+ subset measurements should guide investigators in the design and analysis of clinical trials and epidemiology studies. Ability to obtain improved interlaboratory agreement on CD8+ subset measurements will facilitate further evaluation of these markers in HIV studies.
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PMID:Interlaboratory variability of CD8 subset measurements by flow cytometry and its applications to multicenter clinical trials. NAID/NICHD Women and Infants Transmission Study Group. 758 25

Investigation of common variable immunodeficiency (CVI) is hampered by lack of a suitable in vitro models. We have developed EBV-transformed B lymphoblastoid cell lines from a selected subset of CVI patients and characterized them for phenotypic and functional properties that provide evidence for their representation of the CVI disease state. B cell lines from the patients expressed increased levels of sIgM and reduced levels of sIgD and sIgG. Essentially none of the CVI-derived B cell lines produced IgG and IgA while all produced IgM, in contrast to normal B cell lines that produced large amounts of IgG and IgM and detectable levels of IgA. Expression of CD95 (fas/Apo-1), a molecule that can induce apoptosis, was increased on the CVI B cell lines while CD38, a novel signaling molecule whose stimulation may prevent apoptosis, showed reduced expression. The B cell lines from the CVI patients exhibit increased apoptosis in vitro spontaneously, in response to anti-CD95 mAb and to X-irradiation. These phenotypic and functional changes are similar to findings on freshly derived B cells from the patients. EBV-derived B cell lines from patients with hyper-IgM immunodeficiency and X-linked agammaglobulinemia did not demonstrate increased CD95 expression or enhanced apoptosis. Thus the EBV-derived B cell lines from our selected CVI patients manifest many characteristics of the patients' fresh cells and may provide critical reagents for the further elucidation of the nature of the B cell dysfunction in the selected subset of CVI patients.
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PMID:B cell lines from a subset of patients with common variable immunodeficiency undergo enhanced apoptosis associated with an increased display of CD95 (Apo-1/fas), diminished CD38 expression, and decreased IgG and IgA production. 758 84

The incidence of lymphomas is unusually high in human immunodeficiency virus (HIV)-infected patients. Because cytotoxic T lymphocytes (CTL) represent a major mechanism of the antitumoral immune response in immunocompetent individuals, we asked whether intratumoral activation of CTL was impaired in acquired immune deficiency syndrome (AIDS) lymphomas. Immunohistochemical experiments showed that in AIDS lymphomas intratumoral CD8-positive T lymphocytes accumulated and expressed the TIA-1 antigen, a marker of cytotoxic cells. Flow cytometry studies and in situ hybridization of lymphomatous tissue confirmed the differentiation of CD8-positive cells in cytotoxic cells and their activation, as assessed by their expression of CD38 and human leukocyte antigen (HLA) DR markers as well as the perforin and granzyme B genes, which code for two molecules involved in target cell killing. On average, perforin-producing cells were as numerous in AIDS lymphomas (5,647 +/- 2,655 cells/cm2) as in lymphomas from immunocompetent individuals (3,294 +/- 1,544 cells/cm2). The density of activated CD8-positive cells in the 22 AIDS lymphomas tested was not correlated with peripheral CD4-positive cell counts. These results suggest that in AIDS lymphomas the steps of differentiation and activation of cytotoxic CD8-positive cells are not altered by immune deficiency and that they can take place through pathways relatively independent of CD4-positive T lymphocytes. Thus, other mechanisms of immune deficiency should account for the increased frequency of lymphomas in patients with AIDS.
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PMID:Intratumoral activation of CD8-positive cytotoxic lymphocytes in acquired immunodeficiency syndrome lymphomas. 789 Feb 79

Subsets of activated CD8+ lymphocytes defined by membrane expression of the activation antigens HLA-DR and CD38 were counted by three-color flow cytometry in homosexual men who subsequently became seropositive for human immunodeficiency virus type 1 (HIV). Profound CD8+ cell activation was seen in all subjects at seroconversion and 6 and 12 months later. The HLA-DR+ CD38+ CD8+ cell population, which has potent direct HIV cytotoxic T cell activity, was markedly elevated at seroconversion in all subjects. In some men, these levels remained elevated throughout the first year of infection. During the next 5 years, these men had stable CD4+ cell levels, whereas the others did not. Long-term survivors (seropositive for 9 years, > 800 CD4+ cells/mm3) also had elevated levels of this subset, despite few other activated CD8+ cells. Thus, selective elevation of HLA-DR+ CD38- CD8+ cells was a marker of subsequent stable HIV disease.
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PMID:CD8+ lymphocyte activation at human immunodeficiency virus type 1 seroconversion: development of HLA-DR+ CD38- CD8+ cells is associated with subsequent stable CD4+ cell levels. The Multicenter AIDS Cohort Study Group. 793 Jul 17

New fluorescent monoclonal antibody-dye conjugates permit three-color immunofluorescence analysis of leukocytes in whole blood using a single laser flow cytometer. The fluorochrome used in this study is a tandem conjugate of phycoerythrin (PE) and Cyan-5, which is excitable at 488 nm with a maximum in the emission spectrum at > 650 nm and it can be used together with PE and fluorescein isothiocyanate (FITC). The directly labelled monoclonal antibodies are incubated with unseparated anticoagulated blood and subsequently erythrocytes are lysed by a standardized automated procedure. The resulting leukocyte suspension can then be analyzed for three different surface markers in an individual sample of 100 microliters blood. When compared simultaneously with single-color analysis triple-color immunofluorescence yielded identical quantitative and qualitative results on various lymphocyte subpopulations. The efficacy of this method was evaluated by analyzing leukocytes of 42 healthy donors for the following markers: CD3, CD4, CD8, CD14, CD16, CD19, CD25, CD38, CD45RO, CD45RA, CD56, CD57, TCR-gamma/delta and HLA-DR. Of special interest was the finding that CD45RA and CD45RO are differently expressed in CD4 and CD8 cells. The reliability and convenience of this three-color analysis will make it possible to do more sophisticated examinations of subpopulations and their relevance in the monitoring of autoimmune diseases, immunodeficiency syndromes including AIDS and malignant disorders such as leukemias.
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PMID:Triple immunofluorescence flow cytometry, using whole blood, of CD4+ and CD8+ lymphocytes expressing CD45RO and CD45RA. 810 28

We have established a cell line (DS-1) of B-cell lineage in long-term culture. It was derived from an immunodeficient patient with intestinal lymphangiectasia and lymphoma by culturing malignant pleural effusion cells with IL-6 in vitro. The cell surface phenotype was; PCA-1, HLA Class II(+); CD25, CD19, CD20, CD30, CD38(-). Cell proliferation was poor in medium and exhibited an eight-fold, dose-dependent increase of proliferation in response to rIL-6 of human but not murine origin. The secretion of IgG into culture supernatants by DS-1 was not enhanced by rIL-6. While constitutive production of IL-6 was not detected by bioassay using murine B9 hybridoma cells or by ELISA, the presence of IL-6 message was detected in polyA+ selected mRNA by Northern analysis. Spontaneous proliferation of DS-1 cells was inhibited by neutralizing polyclonal antibodies to IL-6 (37%) and mAb to IL-6 (54%) and IL-6R (53%). DS-1 expressed both high and low affinity IL-6 receptors (Kd 1.2 x 10(-11) and 6.7 x 10(-10), respectively) by radiolabelled binding and Scatchard analysis. Thus, DS-1 represents an autocrine IL-6-producing cell line of B-cell lineage which resembles lymphoid malignancies arising in patients with AIDS and other immunodeficiency diseases. Despite constitutive IL-6 production, the in vitro growth of DS-1 is dependent upon exogenous IL-6. DS-1 may thus be useful as a model of IL-6 dependency. This cell line may also facilitate development of strategies for diagnosis and treatment of B-cell lymphomas in immunocompromised patients.
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PMID:Characterization of a new IL-6-dependent human B-lymphoma cell line in long term culture. 814 4

High-grade B-cell-type non-Hodgkin's lymphomas are observed in 5% to 8% of patients positive for the human immunodeficiency virus. Nearly all cases belong to one of the three major histologic types: centroblastic or large noncleaved cell, immunoblastic and Burkitt's lymphoma, or small noncleaved cell. Some cases that are polymorphic are termed high-grade B-cell, not otherwise specified (NOS). The authors determined the immunophenotype of each histologic category of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkins' lymphoma and sought a relationship with the presence of the Epstein-Barr virus (EBV). B-cell differentiation antigens, activation marker expression (human leukocyte antigen-DR, CD10, CD19, CD20, CD21, CD22, CD23, CD25, CD30, CD38), and epithelial membrane antigen were analyzed. The clonality was determined by the detection of cytoplasmic immunoglobulin, surface immunoglobulin, and the analysis of joining region (JH) immunoglobulin gene configuration by Southern blot. Epstein-Barr virus was detected either by Southern blot analysis using BamHI W probe fragment or by in situ hybridization with EBV-encoded RNA transcripts-1 specific probe. The immunophenotypic and genotypic results were compared with the morphology results and with the presence or absence of EBV. Burkitt's lymphomas were associated with EBV in 50% of cases, were monoclonal, and expressed mostly immunoglobulin (Ig) MK, CD10, CD19, CD20, CD22, and CD38. This immunophenotypic profile closely resembled those of the centroblastic cases (large noncleaved cell), in which EBV was absent. Epstein-Barr virus was associated with 90% of immunoblastic cases, and only CD10, CD20, and CD38 were expressed. CD71 was expressed in all categories of non-Hodgkin's lymphoma, and CD21 and CD23 were rarely expressed. Two cases of immunoblastic lymphoma and one case of high-grade B-NOS were polyclonal regarding JH rearrangement, but EBV tested with 1.9-Kb Xhol fragment was clonal. No significant immunophenotypic changes were noted in relation to the presence of EBV. Such studies comparing morphology, immunophenotype, and genotype could help classify and better understand the pathogenesis of AIDS-related non-Hodgkin's lymphoma.
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PMID:Immunophenotypic and genotypic analysis of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas. Correlation with histologic features in 36 cases. French Study Group of Pathology for HIV-Associated Tumors. 820 68

Patients undergoing BMT have a long-lasting defect of B cell-mediated immunity, especially if chronic GVHD ensues. It has been postulated that the post-transplant B cell abnormalities can be explained by the recapitulation of B cell ontogeny. To test this hypothesis, we studied the quantitative and phenotypic reconstitution of circulating B cells in 24 transplant recipients and compared it with normal ontogeny. The results confirm that a second round of ontogeny occurs in transplant recipients without chronic GVHD. This was evidenced by the pattern of quantitative B cell reconstitution (low-->high-->normal B cell counts), large B cell size and a high proportion of B cells overexpressing CD38, membrane IgM (mIgM) and membrane IgD (mIgD). The recapitulation of ontogeny was blunted in most patients with chronic GVHD, as evidenced by the absence of the overshoot of total B cells and by the relative lack of CD38high, mIgMhigh and mIgDhigh B cells. We conclude the post-transplant B cell development in patients without chronic GVHD parallels ontogeny. The limited ability of patients with chronic GVHD to re-enact B cell ontogeny may contribute to their longer-lasting and more severe humoral immunodeficiency.
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PMID:B cell reconstitution after human bone marrow transplantation: recapitulation of ontogeny? 827 39

CD38, a molecule with multilineage distribution but unknown function, and the MHC class II molecule HLA-DR (DR) have markedly elevated levels of expression on CD8+ cells of HIV-infected people. This study investigated the expression of CD38 and DR Ag on circulating HIV-specific CD8+ CTL in HIV-seropositive subjects. Purified CD8+ lymphocytes from 22 participants in the University of California at Los Angeles Multicenter AIDS Cohort Study were screened for CTL activity against autologous EBV-immortalized lymphoblast targets infected with vaccinia vectors that carried HIVIIIB gag, pol, and env genes. Sixty-seven percent (14 of 21), 64% (14 of 22), and 9% (2 of 22), respectively, of the subjects had HIV-specific CD8+ CTL activity against gag, pol, and env proteins. CD8+ cells from 11 of the subjects who had high CTL activity were then FACS-separated using three-color immunofluorescence sorting. Circulating DR-CD38- CD8+ cells had little activity. Highly purified DR+CD38+ CD8+ cells had higher HIV-specific CTL activity than other CD8+ cells. DR+CD38- or DR-CD38+ CD8+ cells also mediated significant activity, but only about half as much on a per cell basis as DR+CD38+ CD8+ cells. This is the first report that the CD38 molecule is expressed in vivo on Ag-specific CD8+ CTL, and confirms previous reports that DR is expressed on these cells. Both asymptomatic HIV-seropositive subjects (144 +/- 132/mm3) and AIDS patients (253 +/- 178/mm3) had markedly elevated levels of DR+CD38+ CD8+ cells compared with the levels in HIV-seronegative controls (7 +/- 3/mm3). However, the level of anti-HIV CTL activity was not correlated with the level of DR+CD38+ CD8+ cells, indicating that enumeration of this lymphocyte population by flow cytometry most likely will not be a useful surrogate for measuring functional CTL activity. Low levels of HIV-specific CTL activity, especially against gag, were correlated with lower CD4+ cells numbers, suggesting that the loss of CD8+ T cell cytotoxic activity against HIV that has been reported to occur with advancing HIV disease progression may reflect in part the extent of CD4+ cell immunodeficiency in HIV-infected subjects.
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PMID:Circulating HIV-specific CD8+ cytotoxic T cells express CD38 and HLA-DR antigens. 845 74

Effects of a human immunodeficiency virus (HIV) type 1 protease inhibitor, ritonavir, were evaluated in 21 patients enrolled in a phase I/II study. The magnitude and rates of CD4 and CD8 lymphocyte increase, changes in subsets of CD4 and CD8 lymphocytes, and proliferative responses to mitogen and antigens were analyzed. Significant increases were noted in CD4 and CD8 lymphocyte counts; numbers of CD4CD45RO lymphocytes increased significantly by week 1 of therapy. Increases in the CD4CD45RA subset were observed at week 4. Reductions in the percentage of CD4 and CD8 lymphocytes expressing CD38 were noted. Increases in proliferative responses to phytohemagglutinin were noted in 6 of 7 patients and correlated with duration of virus load suppression. Increased responses to recall antigens and to HIV-specific proteins were observed. Treatment with ritonavir produced alterations in the immune system that included changes in T cell subset distribution and increases in CD4 and CD8 lymphocyte numbers and of lymphocyte function.
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PMID:Alterations in the immune response of human immunodeficiency virus (HIV)-infected subjects treated with an HIV-specific protease inhibitor, ritonavir. 856 92


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