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

A panel of human hematopoietic cell lines was genetically engineered to express recombinant complement receptor 2 (CR2 or CD21), which is also the Epstein-Barr virus (EBV) receptor. The panel was composed of SupT1, J1.1, and U1.HIV cells. The latter is a promonocytic cell line, whereas the other two are T lymphocytic cell lines. J1.1 and U1.HIV cells are latently infected by human immunodeficiency virus type 1 (HIV-1). These three cell lines were transduced with a murine leukemia virus (MLV)-based retroviral vector system. CR2 was efficiently and consistently expressed on the cell membranes, conferring enhanced susceptibility to EBV infection. The efficient expression of recombinant CR2 in cell lines of hematopoietic origin allowed for study of the interaction between EBV infection and HIV-1 gene regulation in suitable cell-culture models. The effects of EBV and HIV-1 coinfection results were cell-type dependent. In the two T lymphocytic cell lines, HIV-1 expression was rapidly and persistently down-regulated by EBV. Conversely, in the promonocytic cell line U1.HIV-CR2, HIV-1 expression was transiently enhanced by EBV. The EBV and HIV-1 coinfection result in U1.HIV-CR2 cells is potentially important, as the activation of HIV-1 gene expression in monocyte-like cells may play a crucial role in the mechanism of CD4+ T cell depletion by apoptosis. Therefore, the U1.HIV-CR2 cell line may represent a useful cell-culture system to study the synergism between EBV and HIV-1 in inducing apoptosis in primary CD4+ T cells.
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PMID:Differential effects on HIV-1 gene regulation by EBV in T lymphocytic and promonocytic cells transduced to express recombinant human CR2. 934 4

We describe the histopathological, immunohistochemical, and molecular characterization of a lymphoma arising in a 7-year-old cat following experimental infection with feline immunodeficiency virus (FIV). The tumor was high grade and of B-cell lineage. The transformed cell had an immature phenotype (CD79a+, CD79b-, CD21-, immunoglobulin heavy and light chain negative), confirmed by antigen receptor gene analysis, which showed germ line configuration. Single-copy, clonally integrated FIV provirus was detected in tumor genomic DNA. FIV p24 antigen was not detected in tumor cells by immunostaining. This study provides the first evidence that the feline lentivirus may play a direct role in cell transformation under certain circumstances.
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PMID:Molecular and immunophenotypical characterization of a feline immunodeficiency virus (FIV)-associated lymphoma: a direct role for FIV in B-lymphocyte transformation? 942 Feb 84

Patients with HIV infection are at high risk for the development of high-grade B-non-Hodgkin's lymphoma (B-NHL). The aim of this study was identification of a predictive diagnostic marker for HIV-associated B-cell lymphomas, using simian-immunodeficiency-virus (SIV)-infected Rhesus monkeys as a well-established in vivo model of HIV-associated lymphomagenesis. We infected 26 monkeys (Macaca mulatta) with SIVmax and measured serum levels of sCD23 longitudinally until necropsy. Of the 26 monkeys, 9 developed high-grade B-NHL, which was preceded by lymphadenopathy (NHL+/LA+) (group 1). Among the 17 animals that remained without clinical evidence of lymphoma during the observation period, 8 developed LA (group 2) and 9 were NHL- and LA-negative (NHL-/LA-) (group 3). Elevation of sCD23 serum levels preceded B-cell lymphoma development, with a median of 44 U/ml in group 1 vs. 7 U/ml and 8 U/ml in groups 2 and 3 respectively, 32 weeks after infection. Differences in the serum level of sCD23 between group 1 vs. groups 2 and 3 became statistically significant 32 to 56 weeks after infection. At necropsy, serum levels of sCD23 were significantly higher in group 1 than in group 2 or group 3; 6/6 samples of SIV-associated B-NHL were positive for gene transcription of CD23 and its receptor CD21 as assessed by RT-PCR. The data point to a potential role of sCD23 as a predictive marker for the development of HIV-associated B-NHL. Moreover, the in vivo model of SIV-infected monkeys suggests the possibility of exactly analyzing the pathobiological role of sCD23 in the lymphomagenesis of SIV-associated B-NHL.
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PMID:Elevated serum level of soluble CD23 precedes development of B-non-Hodgkin's lymphoma in SIV-infected Rhesus monkeys. 968 7

Kaposi's sarcoma (KS) is a vascular tumor predominantly found in the immunosuppressed. Epidemiologic studies suggest that an infective agent is the etiologic culprit. Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus-8 (HHV-8), is a gamma human herpesvirus present in all epidemiologic forms of KS and also in a rare type of a B cell lymphoma, primary effusion lymphoma (PEL). In addition, this virus is present in most biopsies from human immunodeficiency virus (HIV)-associated multicentric Castleman's disease (MCD). MCD is a lymphoproliferative disorder with, like KS, a prominent microvasculature. The genome of KSHV contains the expected open reading frames (ORFs) encoding for enzymes and viral structural proteins found in other herpesviruses, but it also contains an unprecedented number of ORFs pirated during viral evolution from cellular genes. These include proteins that may alter cellular growth (e.g., Bcl-2 and cyclin homologs), induce angiogenesis (e.g., chemokine, chemokine receptor, and cytokine homologs), and regulate antiviral immunity (e.g., CD21 and interferon regulatory factor homologs). No ORF with sequence similarity to the Epstein-Barr nuclear antigens (EBNAs) and latent membrane proteins (LMPs) of Epstein-Barr virus (EBV) is present, but proteins analogous to these in structure and in latent expression are found [e.g., ORF 73 encoding for KSHV latent nuclear antigen (LNA-1) and K12 encoding for a possible latent membrane protein]. Current serologic assays confirm the strong association of infection with KSHV and risk of KS development. The mechanism of how this new virus may trigger the precipitation of KS is still unclear.
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PMID:Kaposi's sarcoma-associated herpesvirus. 970 7

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations of Bruton tyrosine kinase (Btk); Btk plays an essential role in the development of mature B cells. However, small numbers of B cells ("leaky B cells") are present in the peripheral blood of most XLA patients. In this study, we analyzed the function of these leaky B cells obtained from XLA patients. Enough numbers of B cells were available for analysis from five of nine XLA patients originally screened. Sequence analysis revealed missense mutations of Btk in four of the five XLA patients. No mutation was found in the coding region of Btk in one patient. Western blotting and/or flow cytometric analysis failed to detect Btk protein in all five patients. B cells isolated from peripheral blood of these XLA patients were CD5-, CD20+, CD19+, and CD21-. If stimulated with anti-CD40 and IL-4, XLA B cells proliferated normally and produced significant amounts of IgE. Anti-CD40 stimulation of XLA B cells resulted in normal expression of CD23. In addition, three of the five XLA patients studied were immunized with bacteriophage phiX174 and produced low but detectable levels of antiphage-specific Ab. Similarly, X-linked immunodeficiency mice, which carry a missense mutation in Btk, produced substantial amounts of antiphage Ab. These results indicate that CD40 signaling is intact in B cells lacking demonstrable Btk, and that leaky B cells in XLA patients can proliferate, undergo isotype switching, and differentiate into specific Ab-producing cells.
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PMID:Functional analysis of peripheral blood B cells in patients with X-linked agammaglobulinemia. 978 Jan 59

The phenotypic analysis of human umbilical cord blood (CB) mononuclear cells is important to study their maturity and differentiation regarding their transplantable capacity. In this work we have studied differential expression of B cell antigens on CD5-/HLA-DR+ B cells (B1b, B2) and CD5+/HLA-DR+ cells (Bla) from the CB (n=6) and adult peripheral blood (PB) (N=6). CD5-PE, HLA-DR-PerCP and FITC labelled anti-B cell MoAb panel of the 6th International Workshop on Human Differentiation Antigens were used for detection of B cell subpopulations. FacsCalibur (B-D) flow cytometer was used for evaluation of samples. CB Bla (CD5/HLA-DR++) cells proved to be positive with CD9, CD19, CD20, CD21, CD22, CD23, CD24, CD32, CD39, CD45RA, CD76, CD79, MHC-II, IgM and anti Ig light chains MoAbs. CB B1b (CD5-/HLA-DR+) cells reacted with CD9, CD19, CD20, CD21, CD22, CD23, CD24, CD32, CD39, CD45RA, CD79, MHC-II, and IgM MoAbs. PB B cells (B2) expressed CD19, CD20, CD21, CD22, CD24, CD32, CD37, CD39, MHC-II and CD79 Ags. Unlike to the PB the CB B lymphocytes proved to be predominantly B1 cells representing a new-born B cell repertoire. Besides expressing many B cell antigens both the CB Bla and B1b cells showed CD9+, CD45RA+, IgM+ immature, "naive" B cell phenotype. Functionally, B1 cells are capable producing polyreactive IgM and natural autoantibodies but not IgG. This antibody profile might be insufficient regarding the recipient humoral immune defense result in more severe immunodeficiency after CB transplantation.
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PMID:Immunophenotypic characterisation of cord blood B-lymphocytes. 991 47

Lymphoid hyperplasia of Waldeyer's ring (WR) is an often-symptomatic complication of human immunodeficiency virus (HIV) infection. A characteristic but not well explained finding is the presence of multinucleated giant cells (MNGCs) adjacent to crypt or surface epithelium. To further elucidate the MNGCs and assess their relationship to HIV and Epstein-Barr virus (EBV), 12 specimens from 11 HIV-positive patients were stained with antibodies to HIV-1 p24, EBV (latent membrane protein, LMP-1), histiocytes (CD68), and other antigen-presenting cells: S-100 protein, the Langerhans cell (LC) marker CD1a, and the follicular dendritic cell (FDC) marker (CD21). Double immunofluorescent staining to assess co-expression of p24 and cell-specific markers was performed and analyzed by laser-scanning confocal microscopy with 3-dimensional reconstruction. In situ hybridization for EBV-encoded small RNA (EBER) was performed in all cases. Immunostains showed MNGCs labeled for p24, S-100, and CD68, but not CD1a. In 1 case, rare MNGCs were CD21-positive. EBV LMP-1 was uniformly negative, although EBER-positive lymphocytes were seen by in situ hybridization in 9 of 12 specimens (numerous in only 3 specimens). Double immunofluorescent staining showed co-localization of p24 with CD68 and S-100. Our results suggest that MNGCs are generally HIV-infected, EBV-negative, and most likely represent an unusual S-100-positive histiocyte subset (not LC or FDC). Their exact pathophysiologic role remains uncertain. EBV does not appear to play a major role in the pathogenesis of WR lymphoid hyperplasias in HIV infection.
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PMID:HIV-associated Waldeyer's ring lymphoid hyperplasias: characterization of multinucleated giant cells and the role of Epstein-Barr virus. 1057 22

Immunodeficiency-related B-cell disorders are seen after organ transplantation and in congenital and acquired immunodeficiency states. Post-transplant lymphoproliferative disorders (PTLD) comprise a histologic spectrum ranging from hyper-plastic appearing lesions to frank non-Hodgkin's lymphoma or multiple myeloma histology. Multiple clones may co-exist, representing a uniquely different mechanism for lymphomagenesis. The incidence varies from 1% in renal recipients to 8% in lung recipients, but can be markedly increased by the use of anti-T-cell therapies, or by T-cell depletion in bone marrow transplantation. Pre-transplant EBV seronegativity increases risk to as high as 30%-50%. More than 90% of tumors are EBV-associated. Mechanisms for viral lymphomagenesis remain incompletely defined; LMP-1 may function as an oncogene and coprecipitates with TRAF, BCL-2 overexpression has also been identified. A possible direct tumorigenic effect has recently been suggested for cyclosporine. PTLD has a highly variable clinical picture, certain patterns are however seen. Reversibility of PTLD with reduction in immunosuppressives has long been recognized. Predicting reversibility has been difficult. The presence or absence of BCL-6 mutations has recently been identified as being of predictive value. Surgical resection can be curative. Cytotoxics, although problematic, can also be curative. Long term remission has been achieved with anti CD21 and CD24 antibodies; efficacy has been reported anecdotally for interferon alpha and for rituximab. In vitro expanded EBV-specific T cells have been effective as treatment and as prophylaxis in the setting of bone marrow transplantation. EBV viral load measured in blood appears to correlate with the emergence of PTLD and may facilitate prophylactic studies. PTLD is a model of immunodeficiency related EBV lymphomagenesis. Pathogenetic, therapeutic, and prophylactic insights gained from the study of PTLD are likely to be applicable to other immunodeficiency states and to EBV-related lymphoid neoplasia in general.
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PMID:Diagnosis and treatment of transplant-related lymphoma. 1070 78

After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells of an individual in the presymptomatic stage. Although they did so at a lower efficiency, these antibodies were able to remove HIV from tonsillar cells of patients under highly active antiretroviral therapy, suggesting that the C3d-CR2 interaction remains a primary entrapment mechanism in treated patients as well. In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus, targeting CR2 may facilitate new approaches toward a reduction of residual virus in GC.
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PMID:Detachment of human immunodeficiency virus type 1 from germinal centers by blocking complement receptor type 2. 1093 8

Post-transplant lymphoproliferative disorders (PTLD) share many of the features of human immunodeficiency virus (HIV)-related lymphomas, although important differences exist. PTLD ranges from hyperplastic lesions to aggressive lymphoma or multiple myeloma histology. The coexistence of multiple clones, and the strong association with the Epstein-Barr virus (EBV), represent a uniquely different mechanism for lymphomagenesis when compared with de novo lymphoma. The risk of PTLD increases as the duration of immunodeficiency lengthens, with unusual, newly described entities arising after prolonged immunosuppression. The risk is also strongly influenced by the specific anti-T-cell therapies used to prevent graft rejection, providing insight into the nature of immune surveillance. The presence or absence of bcl-6 mutations may be predictive of the reversibility of the PTLD with reduction in immunosuppressive therapy. The use of cytotoxic agents has been complicated by problems similar to those encountered with HIV-related lymphomas, but can nonetheless be very effective. Long-term remission has been achieved with anti-CD21 and anti-CD24 antibodies, although these have not been equally effective for all categories of PTLD. In vitro-expanded EBV-specific T cells have been effective both as treatment and as prophylaxis in the setting of PTLD occurring after marrow transplantation. EBV viral load measurement correlates with the emergence of PTLD, and may make clinical trials of screening, prophylaxis, or early intervention possible.
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PMID:Transplantation-related lymphoproliferative disorder: a model for human immunodeficiency virus-related lymphomas. 1095 Mar 66

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