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)

We previously demonstrated that IL-2 promotes the adhesion of NK cells to endothelial cells (EC) and that EC are readily lysed by lymphokine-activated killer (LAK) cells in vitro, suggesting that cell mediated endothelial injury may contribute to the capillary leak syndrome observed in patients treated with IL-2. In this investigation, we sought to determine the effects of EC activation on the in vitro susceptibility of EC to LAK cell-mediated cytolysis. Despite increased binding of CD16+ lymphocytes to TNF-activated EC monolayers, prior exposure of EC to any of several IL-2-inducible cytokines including TNF-alpha, IL-1 beta, and IFN-gamma not only failed to render the EC more vulnerable to cytolysis but increased their resistance to LAK cells in 111Indium release cytolysis assays. This decrement in susceptibility to cytolysis resulting from prior exposure to cytokines preceded any detectable increase in HLA class I or II Ag expression. In cold target competition experiments with LAK cell effectors and radiolabeled K562 target cells, TNF-primed EC were no more competitive than unstimulated EC, and in assays with unstimulated PBMC effectors, the addition of unlabeled TNF-activated EC actually increased the cytolysis of the radiolabeled tumor cells. The effects of various cytokines and lymphocyte preparations on EC permeability were also evaluated. In these experiments, saphenous vein EC were cultured on porous filter disks, exposed to cytokines or lymphocytes, and the diffusion of 125I-BSA through the filters was then measured. Exposure to IL-2, IFN-gamma, or TNF-alpha did not increase the diffusion of the BSA through the EC-coated filters, whereas LAK cells markedly increased their permeability. Consistent with the results of the cytolysis assays, pretreatment of the EC with TNF, IL-1, or IFN-gamma diminished the LAK cell-induced increase in BSA diffusion. These results suggest that although circulating IL-2-inducible cytokines such as TNF and IFN-gamma may activate EC in vivo and contribute to lymphocyte margination and lymphopenia, they may not be directly responsible for the IL-2-induced capillary leak syndrome and may actually protect EC from LAK cell-mediated injury.
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PMID:Activated endothelial cells resist lymphokine-activated killer cell-mediated injury. Possible role of induced cytokines in limiting capillary leak during IL-2 therapy. 252 94

Antilymphocyte antibodies have been demonstrated in autoimmune diseases, acute viral infections, and acquired immune deficiency syndrome (AIDS) by using either the conventional microlymphocytotoxicity or the double fluorescence technique. In the present study, we used both methods to detect the antilymphocyte antibodies and to characterize further their immunologic significance in patients with AIDS and their sexual partners. The results using the conventional microlymphocytotoxicity method demonstrated that 8 of 10 patients with AIDS and 6 of 10 partners had significant levels of antilymphocyte antibodies which were reactive with B and T cells at cold and warm temperatures. A significant loss in antibody activity following absorption with B, T, and Daudi cells and Staphylococcus aureus, but not platelets or red cells, indicated that these antibodies are not directed to HLA class I antigens but, rather, to antigens that are common to both groups of lymphocytes. There is a close association between antilymphocyte antibodies and lymphopenia in patients but not in partners. Antibodies against lymphocyte subclasses [helper (T4) and suppressor (T8)] were detected by the double fluorescence staining technique, which employs C6-deficient serum as a nonlytic source of complement, and demonstrated the binding of antibodies to target cells, in contrast to lysing of the target cells as in the microlymphocytotoxicity method. The results of this assay showed that antibodies were directed to both populations, and there was no correlation or association between the absolute numbers of peripheral T4 and T8 cells and the percentage of antibody binding. Taken together, there appear to be at least two kinds of antilymphocyte antibodies: lymphocytotoxic antibodies detected by the conventional microlymphocytotoxicity assay and noncytotoxic antibodies detected by the double fluorescence staining technique. The former may be responsible in part for the lymphopenia. The latter may alter lymphocyte function. The patients and partners who had antilymphocyte antibodies also had anti-HTLV-III antibodies, although there was not any close correlation between titers. These findings support the possibility that both types of antibodies occur as part of a generalized immune response, possibly stimulated by the same viral agent.
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PMID:The significance of antilymphocyte antibodies in patients with acquired immune deficiency syndrome (AIDS) and their sexual partners. 303 11

A subgroup of common variable immunodeficiency (CVID) patients have distinct clinical features, particularly granulomata splenomegaly, characteristic blood lymphocyte phenotype, and elevated circulating TNF levels. To investigate the genetic basis for this phenotype, 150 CVID patients and 200 controls were genotyped for six biallelic TNF and lymphotoxin-alpha (LT alpha) polymorphisms and eight class I and II HLA loci using PCR and sequence specific primers (PCR-SSP) sequence-specific primers. Clinical and immunophenotypic data were collected for 90 patients to examine associations with CVID patient subgroups. The presence of granulomata (22% of patients) was strongly associated with splenomegaly, T and B lymphopenia, reduced CD4+ CD45RA+ T cells, and CD8+ CD57+ lymphocytosis, confirming the concept of a subgroup of patients with distinct clinical and laboratory features. The uncommon TNF +488A allele was strongly associated with this subgroup (p = 0.0005). The association between "granulomatous" CVID and TNF +488A was independent of HLA class I and II associations. We postulate that the presence of the TNF +488A allele, or alleles in linkage disequilibrium with it, contributes to the high levels of TNF and granulomatous complications characteristic of this subgroup of patients.
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PMID:TNF and lymphotoxin-alpha polymorphisms associated with common variable immunodeficiency: role in the pathogenesis of granulomatous disease. 955 Apr 27

Human herpesvirus 6 (HHV-6) has a tropism for T lymphocytes and monocytes/macrophages, suggesting that HHV-6 infection affects the immunosurveillance system. In the present study, we investigated the HHV-6-induced phenotypic and functional alterations of dendritic cells (DCs), which are professional antigen-presenting cells. HHV-6 infection of monocyte-derived immature DCs appeared to induce the up-regulation of CD80, CD83, CD86, and HLA class I and class II molecules, suggesting that HHV-6 infection induces the maturation of DCs. In addition, the antigen capture capacity of DCs was found to decrease following infection with HHV-6. In contrast to up-regulation of mature-DC-associated surface molecules on HHV-6-infected DCs, their capacity for presentation of alloantigens and exogenous virus antigens to T lymphocytes decreased significantly from that of uninfected DCs. In contrast, there appeared to be no reduction in the capacity for presentation of an HLA class II-binding peptide to the peptide-specific CD4(+) T lymphocytes. These data indicate that HHV-6 infection induces phenotypic alterations and impairs the antigen presentation capacity of DCs. The present data also suggest that the dysfunction of HHV-6-infected DCs is attributable mainly to impairment of the antigen capture and intracellular antigen-processing pathways.
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PMID:Phenotypic and functional alterations of dendritic cells induced by human herpesvirus 6 infection. 1223 10

Approximately 30% of patients with hemophilia in Japan were infected with human immunodeficiency virus (HIV) in early 1980s through contaminated blood products. In 1995, a cohort of HIV-infected, asymptomatic patients with hemophilia was set up for follow-up study. Although the patients met the criteria for long-term non-progressor (LTNP) at the entry to the cohort, some of them later developed lymphopenia during five more years of observation. We collected blood samples from 80 long-term survivors; 42 of them did not require antiviral therapy, but the rest were under treatment. Analysis of HLA-B genotype revealed that carriers of known HIV-resistant alleles such as HLA-B*5701, B*5801, and alleles of B27 antigenic group were not increased in frequency, but that HLA-B*1507 was increased in the cohort (6.25% vs. 1.03%, OR = 6.40, p = 0.039). We also observed the decrease in carriers of HLA-B*5401 (3.75% vs. 14.95%, OR = 0.22, p = 0.016). HLAB* 5401 is a relatively common allele in East Asian populations and belongs to the same B22 antigenic group as B55 and B56 which were reported to associate with rapid progression. Our data indicated that HLA class I is one of the host factors involved in the retardation of HIV disease progression as also reported in the previous studies; however, the alleles associated with this resistance were not the same because of divergent host genetic background.
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PMID:HLA-B polymorphism in Japanese HIV-1-infected long-term surviving hemophiliacs. 1621 28