Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical manifestations of AIDS are predominantly due to the cellular and humoral immune dysfunction caused by HIV infection, and thymic dysplasia caused by HIV infection probably contributes to the T cell lymphopenia. In the present study, T cell differentiation and/or maturation was assessed when enriched CD34+ stem cells (SCs or SC) purified from bone marrow of HIV-seropositive hemophiliacs were cocultured with allogeneic cultured thymic epithelial fragments (CTEFs). When HIV-seropositive hemophiliacs' enriched CD34+ SC were cocultured with allogeneic CTEFs, acquisition of the T cell phenotypic markers CD7, CD2, CD3, CD4, CD8 and T cell receptor for antigen (TCR) alpha beta was observed from cells harvested from the culture media peaking at approximately 28 days. Origin of the differentiated and matured T cells from the CD34+ SC was confirmed by labeling the SC with 5-(and -6)-(((4-chloromethyl)benzoyl)amino)tetra-methyl-rhodamine (CMTMR), a fluorescent cytoplasmic dye, and detecting fluorescence in the differentiated and matured T cell by flow cytometry. In one experiment, CMTMR labeling was omitted and double positive CD4+CD8+ and triple positive CD3+CD4+CD8+ thymocytes were identified. These studies confirmed that thymocyte differentiation/maturation from SC had occurred. In addition, T cells obtained from the CD34+ SC and CTEF cocultures proliferated to phytohemagglutinin stimulation maximally with stem cell donor antigen-presenting cells (APCs) and also proliferated to pooled B cells in a mixed lymphocyte culture (MLC). Furthermore, the T cells produced were tolerant to thymus donor B cell HLA antigens (p < 0.025); though there was slight MLC reactivity to autologous stem cell donor B cell HLA compared to thymic B cells (p < 0.025). These T cells demonstrated positive self-alloreactivity to stem cell HLA antigens in four of nine persons, though decreased compared to pool B cell alloantigens. Furthermore, in three experiments, responsiveness to stem cell donor B cells subsequently disappeared upon further duration of CD34+ SC-CTEF coculture. These studies suggested that CD34+ SC gave rise to accessory cells populating the thymus that contributed to HLA restriction. To further evaluate this hypothesis, two different donors of CD34+ SC were cultured simultaneously with thymic epithelial fragments and MLC reactivity was then examined toward APC of the stem cell donors. In these experiments, T cells responded to stimulation with HLA antigens of the pool B cells and did not respond to thymus donor B cells. In six of eight experiments, the chimeric SC-CTEF T cells did not respond to stimulation with B cells of either stem cell donor. These studies suggest that HLA restriction and tolerance were induced by cells of the stem cell donor as well as the thymic epithelial cell HLA antigens. In summary, these studies demonstrated that HIV-infected hemophiliac bone marrow-derived nonadherent CD34+ SC were capable of differentiating and/or maturing into T cells when cocultured in a normal allogeneic thymic environment. Furthermore, the T cells derived from derived CD34+ SC were capable of differentiating into T cells when cocultured in a normal allogeneic thymic environment, proliferated maximally with APCs from the stem cell donor and were tolerant of thymic HLA class II antigens, and to a lesser degree to stem cell donor B cell HLA antigens.
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PMID:T cell differentiation/maturation of CD34+ stem cells from HIV-seropositive hemophiliacs in cultured thymic epithelial fragments. 882 Sep 59

An important place in the immune network is reserved for specific interactions between regulatory antibodies (Ab) and their ligands on T and B lymphocytes. Several lines of evidence indicate that the CD4 glycoprotein may be recognized by such Ab. High levels of CD4-reactive Ab occur in approximately 10-20% of HIV-infected patients. Moreover, between 20 and 30% SLE patients have Ab preferentially reactive with the CD4+ T cells. In relation to this, we have done studies aimed at demonstrating the existence and characteristics of Ab directly targeting CD4 in patients with SLE in comparison with rheumatoid arthritis and normal controls. Assessment of the CD4-reactive Ab by different approaches revealed a several-fold increase in serum concentration of anti-CD4 Ab restricted to a subset of SLE patients (n = 15/87, 17.2%). Enhanced binding was shown to occur specifically both on native CD4 (by immunofluorescence) and on recombinant CD4 (by ELISA and Western blot). Anti-CD4 Ab belonged to IgM and/or IgG isotypes. The overall binding of immunoglobulins to the CD4 molecule was not significantly contributed by DNA/anti-DNA and other circulating immune complexes, and there was no restriction in the usage of kappa and lambda light chains. Clinically, high CD4 reactivity occurred in SLE patients with active disease, as measured by the SLEDAI, and was associated with particular clinical manifestations, including neuropsychiatric disease and lymphopenia.
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PMID:CD4-reactive antibodies in systemic lupus erythematosus. 883 74

We reviewed the clinical features and risk factors for Pneumocystis carinii pneumonia (PCP) in patients with brain tumors (BTs) seen at our institution between 1980 and 1992. Previously rare, this opportunistic infection appears to be increasing among HIV-negative cancer patients receiving immunosuppressive medications. Recent reports have noted PCP among BT patients receiving corticosteroids, and suggested that these patients are particularly likely to develop PCP when corticosteroids are tapered. Nine BT patients, eight with high-grade gliomas, experienced ten episodes of PCP. None were known HIV-positive. All were on dexamethasone (DXM) at PCP onset, and had continuously been receiving it for 47-398 days (median 69). Daily DXM dose at PCP onset ranged from 1-16 mg (median 9). Five episodes occurred in patients receiving a stable DXM dose and five during DXM taper. Nine episodes occurred in patients receiving chemotherapy. All patients had absolute lymphopenia at PCP onset, ranging from 80-900 x 10(6) lymphocytes/l (median 222 x 10(6)/l, normal > 1000 x 10(6). Three episodes were fatal despite appropriate antibiotic therapy. Unlike others, we did not find that corticosteroid taper predisposed to developing PCP. As in HIV, PCP in BT patients appears related to lymphopenia, in these patients attributable to use and duration of corticosteroids and in some cases cytotoxic chemotherapy. Effective prophylaxis exists and should be considered for lymphopenic patients and those requiring DXM for > five weeks.
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PMID:Pneumocystis pneumonia in brain tumor patients: risk factors and clinical features. 884 57

During measles virus (MV) infection, lymphopenia and immune suppression are observed in humans, yet the mechanisms underlying these effects remain unknown except that membrane cofactor protein (MCP, CD46) acts as a receptor for MV, accelerating entry of the virus into host cells. CD46 is a complement regulator, the role of which is to protect host cells from the autologous complement system. Thus, it encompasses complement-related and MV-mediated immune modulation. In this review, I discuss the structural and functional differences between CD46 on lymphocytes and on granulocytes, which partly explain the higher susceptibility of lymphocytes to MV than other blood cells to clarify the mechanisms of MV-mediated lymphopenia and immune suppression, and help resolve the T cell immunity dysfunction secondary to virus infection including HIV.
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PMID:CD46, a complement regulatory protein/measles virus receptor, and its relation to hematological disorders. 885 67

We report a 65-year-old Japanese woman with Kaposi's sarcoma (KS). The eruption first occurred on the legs while she was admitted for treatment of poorly differentiated lung cancer. Approximately eight months after the evolution, cutaneous tumors rapidly spread to the forearms, trunk, and pharynx. At that time, the patient had received systemic corticosteroid (10-40 mg/day of prednisolone) for about three months to reduce pulmonary inflammation. The laboratory data showed anemia, lymphopenia, hypogammaglobulinemia, and a decreased T cell count, although the serological test for HIV infection was negative. The patient was treated with radiation (X-ray for KS of pharynx and electron beam for KS of lower legs) and local intralesional injection of vinblastine. Although both therapies were very effective and well tolerated, she died of bacterial pneumonia and sepsis. Autopsy revealed KS tumors, unknown before death, in both lungs, the esophagus, and the stomach. The left lung cancer had disseminated and metastasized to the right lung, pleura, mediastinum, and abdominal cavity. It is suspected that chronic respiratory distress and systemic use of corticosteroids might have induced the rapid extension of KS.
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PMID:Kaposi's sarcoma associated with lung cancer and immunosuppression. 885 91

IL-2 administration in vivo has been shown to increase CD4+ T cell counts in HIV+ patients. We have previously reported that PBMC from HIV-infected patients undergo marked spontaneous apoptosis in vitro. In this study, we examined the effect of IL-2 added in vitro upon culture-induced apoptosis in PBMC from 80 HIV-infected patients by flow cytometry. IL-2 at concentrations of > or = 10 U/ml significantly reduced spontaneous apoptosis in CD3+ T lymphocytes in patients but not in healthy volunteers. Interestingly, we observed that Bcl-2 expression in patient lymphocytes decreased rapidly upon in vitro culture while that in cells of healthy volunteers was relatively unaffected. The most significant decrease in Bcl-2 expression was noted in the apoptotic cell population. The IL-2-mediated reduction in lymphocyte apoptosis was found to be associated with the blocking of this culture-induced down-modulation of Bcl-2 expression. IL-2 did not induce significant expansion of lymphocytes during the culture period nor did it affect Fas Ag expression in patient cells, which were already expressing Fas maximally. These findings strongly suggest that IL-2 mediates its apoptosis-blocking effects via suppressing down-modulation of Bcl-2. Our findings also provide an experimental basis for the ongoing therapies utilizing this cytokine for slowing HIV disease progression.
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PMID:IL-2 rescues in vitro lymphocyte apoptosis in patients with HIV infection: correlation with its ability to block culture-induced down-modulation of Bcl-2. 889 56

Previous studies have demonstrated that T cell-reactive antibodies in HIV-1 infection contribute to lymphocyte depletion by cytotoxicity that involves differential membrane targets, such as the 43.5-kD receptor on CEM cells. Here, we show that these antibodies bind Fas as result of a molecular mimicry of the gp120. Both flow cytometry and immunoblotting using the human Fas-transfected mouse WC8 lymphoma revealed positive binding of immunoglobulin G from several patients to a 43.8-kD membrane receptor that also reacts with the CH11 anti-Fas monoclonal antibody. Specificity to Fas was further confirmed to chimeric recombinant human Fas-Fc by ELISA, whereas overlapping peptide mapping of a Fas domain (VEINCTR-N) shared by gp120 V3 loop demonstrated a predominant affinity to the full-length 10-mer peptide. Four anti-Fas affinity preparations greatly increased the subdiploid DNA peak of CEM cells similar to agonist ligands of Fas. In addition, anti-Fas immunoglobulin G strongly inhibited the [3H]thymidine uptake of CEM cells in proliferative assays, inducing a suppression as high as provoked by both CH11 mAb and recombinant human Fas ligand. Since anti-Fas were reactive to gp120, it is conceivable that antibodies binding that domain within the V3 region are effective cross-linkers of Fas and increase apoptosis in peripheral T cells. These results suggest that autologous stimulation of the Fas pathway, rather than of lymphocytotoxic antibodies, may aggravate lymphopenia in a number of HIV-1+ subjects.
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PMID:Cross-linking of Fas by antibodies to a peculiar domain of gp120 V3 loop can enhance T cell apoptosis in HIV-1-infected patients. 897 84

After several years of latency, feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) cause fatal disease in the cat. The aim of this study was to determine laboratory parameters characteristic of disease progression which would allow a better description of the asymptomatic phase and a better understanding of the pathogenesis of the two infections. Therefore, experimentally infected cats (FIV and/or FeLV positive) and control animals were observed over a period of 6.5 years under identical conditions. Blood samples were analyzed for the following: complete hematology, clinical chemistry, serum protein electrophoresis, and determination of CD4+ and CD8+ lymphocyte subsets. The following hematological and clinical chemistry parameters were markedly changed in the FIV-infected animals from month 9 onwards: glucose, serum protein, gamma globulins, sodium, urea, phosphorus, lipase, cholesterol, and triglyceride. In FeLV infection, the markedly changed parameters were mean corpuscular volume, mean corpuscular hemoglobin, aspartate aminotransferase, and urea. In contrast to reports of field studies, neither FIV-positive nor FeLV-positive animals developed persistent leukopenia, lymphopenia, or neutropenia. A significant decrease was found in the CD4+/CD8+ ratio in FIV-positive and FIV-FeLV-positive animals mainly due to loss of CD4+ lymphocytes. In FeLV-positive cats, both CD4+ and, to a lesser degree, CD8+ lymphocytes were decreased in long-term infection. The changes in FIV infection may reflect subclinical kidney dysfunction, changes in energy and lipid metabolism, and transient activation of the humoral immune response as described for human immunodeficiency virus (HIV) infections. The changes in FeLV infection may also reflect subclinical kidney dysfunction and, in addition, changes in erythrocyte and immune function of the animals. No severe clinical signs were observed in the FIV-positive cats, while FeLV had a severe influence on the life expectancy of persistently positive cats. In conclusion, several parameters of clinical chemistry and hematology were changed in FIV and FeLV infection. Monitoring of these parameters may prove useful for the evaluation of candidate FIV vaccines and antiretroviral drugs in cats. The many parallels between laboratory parameters in FIV and HIV infection further support the importance of FIV as a model for HIV.
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PMID:Parameters of disease progression in long-term experimental feline retrovirus (feline immunodeficiency virus and feline leukemia virus) infections: hematology, clinical chemistry, and lymphocyte subsets. 900 78

A 67-year-old male was hospitalized because of nonspecific symptoms and bilateral pleural effusions. He gave no history of cough, dyspnea or thoracic pain. The blood counts showed moderate anemia and high-grade lymphopenia. The tuberculin test and the anergy-panel were both negative. Testing for HIV was negative. Analysis of pleural fluid showed an exudate with 47% lymphocytes and absence of acid-fast bacilli on Ziehl-Neelsen smear. On histologic examination, the pleural tissue showed no evidence of granuloma. However, cultures for mycobacteria of pleural tissue yielded M. tuberculosis. In this case of pleural tuberculosis, leading symptoms were absent and the tuberculin test was negative in the presence of active tuberculosis. In addition, the cells in the pleural effusion were not predominantly lymphocytic. Patients presenting with unclear effusion should undergo extensive investigations, including a tuberculin test, and anergy panel, pleural fluid cultures, and pleural biopsy with cultures for microorganisms, with the object of establishing or ruling out pleural tuberculosis.
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PMID:[An unusual presentation of tuberculosis]. 901 35

Decline in blood CD4+ lymphocytes during primary symptomatic infections with HIV is usually attributed to viral killing, and has not been considered in terms of altered lymphocyte migration and sequestration. We therefore sought to examine whether CD4+ cell loss from blood of macaques undergoing an acute primary SIV infection might be due to increased synthesis of cytokines, known to profoundly affect lymphocyte trafficking, rather than to direct lymphocyte destruction by virus. The findings indicate that rapid lymphocyte depletion following acute infection is not selective for CD4+ cells, correlates precisely with increased plasma IFN-gamma and tumor necrosis factor-alpha levels, and is reversible. CD4/CD8 ratios in lymph nodes with high viral burdens remain relatively unchanged despite lymphocyte loss from blood. Levels of cytokine mRNA measured in lymphoid organs reflect neither cytokine plasma levels nor their potential to induce sequestration. These results support a model of cytokine-induced lymphocyte extravasation to account for the acute HIV/SIV-induced CD4+ cell lymphopenia and raise questions regarding the extent to which altered lymphocyte migration plays a role in the gradual CD4+ cell depletion throughout infection.
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PMID:Virus-induced cytokines regulate circulating lymphocyte levels during primary SIV infections. 918 15


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