UMLS:C0021051 - FACTA Search

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

Because the mechanisms associated with recruitment of monocytes to brain in AIDS encephalitis are unknown, we used tissues from rhesus monkeys infected with simian immunodeficiency virus (SIV) to examine the relative contributions of various adhesion pathways in mediating monocyte adhesion to endothelium from encephalitic brain. Using a modified Stamper and Woodruff tissue adhesion assay, we found that the human monocytic cell lines, THP-1 and U937, and the B cell line, Ramos, preferentially bound to brain vessels from monkeys with AIDS encephalitis. Using a combined tissue adhesion/immunohistochemistry approach, these cells only bound to vessels expressing vascular cell adhesion molecule-1 (VCAM-1). Furthermore, pretreatment of tissues with antibodies to VCAM-1 or cell lines with antibodies to VLA-4 (CD49d) inhibited adhesion by more than 70%. Intercellular adhesion molecule-1 (ICAM-1)/beta 2 integrin interactions were not significant in mediating cell adhesion to the vasculature in encephalitic simian brain using a cell line (JY) capable of binding rhesus monkey ICAM-1. In addition, selectin-mediated interactions did not significantly contribute to cell binding to encephalitic brain as there was no immunohistochemical expression of E-selectin and P-selectin in either normal or encephalitic brain, nor was there a demonstrable adhesive effect from L-selectin using L-selectin-transfected 300.19 cells on simian encephalitic brain. These results demonstrate that using the tissue adhesion assay, THP-1, U937, and Ramos cells bind to vessels in brain from animals with AIDS encephalitis using VCAM-1/alpha 4 beta 1 integrin interactions and suggest that VCAM-1 and VLA-4 may be integral for monocyte recruitment to the central nervous system during the development of AIDS encephalitis.
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PMID:Monocyte adhesion to endothelium in simian immunodeficiency virus-induced AIDS encephalitis is mediated by vascular cell adhesion molecule-1/alpha 4 beta 1 integrin interactions. 750

Humans and domestic animals with African trypanosomiasis exhibit abnormalities of immune function characterized by polyclonal lymphocyte activation and, paradoxically, progressive immunodeficiency. Mice infected with Trypanosoma brucei clone IaTat1.2 develop a fulminant parasitemia by day 5 of infection. B lymphocytes isolated from spleens of infected mice display an aberrant activation phenotype manifested by decreased CD23 and surface IgM, increased CD69 and L-selectin, and normal levels of surface IgD, MHC class II, CD32, and transferrin receptor. Kinetic analyses showed that CD23 and surface IgM were continuously down-regulated from day 2 through day 5, whereas MHC class II was elevated on days 2 and 3, but returned to normal levels by day 5, suggesting that CD23 and MHC class II are independently regulated in T. brucei infection. The aberrant activation phenotype of B cells responding in vivo to T. brucei was accompanied by impaired responsiveness of these B cells to mitogenic stimulation in vitro. The pathologic phenotypic and functional properties of B lymphocytes from T. brucei-infected mice can be partially accounted for by the virtual total arrest of B cells in G0/G1A of the cell cycle. The B lymphocyte alterations observed in the present studies provide new insight into the immunopathology of African trypanosomiasis. We propose that terminal infection with T. brucei induces early activation events in host B lymphocytes, but that the activation response becomes aberrant by the development of what seems to be a total block in cell cycle progression.
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PMID:B lymphocytes of mice display an aberrant activation phenotype and are cell cycle arrested in G0/G1A during acute infection with Trypanosoma brucei. 751 10

Impaired polymorphonuclear neutrophil (PMN) function may contribute to the onset of certain life-threatening bacterial and fungal infections in human immunodeficiency virus (HIV)-infected patients. Published data on PMN functional activity in HIV infection are controversial, possibly because most studies have involved PMNs isolated from their blood environment by means of various procedures that may differently affect surface receptor expression and thereby alter cellular responses. We therefore used flow cytometry to study the expression of adhesion molecules at the PMN surface, actin polymerization, and the oxidative burst of whole-blood polymorphonuclear neutrophils in 42 HIV-infected patients at different stages of the disease. These PMNs were activated in vivo, as demonstrated by increased expression of the adhesion molecule CD11b/CD18, reduced L-selectin antigen expression, increased actin polymerization, and increased H2O2 production. The alterations were present in asymptomatic patients with CD4+ cell counts greater than 500/microL and did not increase with the progression of the disease. Stimulation by bacterial N-formyl peptides showed dysregulation of L-selectin shedding and decreased H2O2 production after ex vivo priming with tumor necrosis factor alpha or interleukin-8 (IL-8). These latter impairments, which correlated with the decrease in CD4+ lymphocyte numbers and with IL-8 and IL-6 plasma levels, could contribute to the increased susceptibility of HIV-infected patients to bacterial infections.
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PMID:Polymorphonuclear neutrophils from human immunodeficiency virus-infected patients show enhanced activation, diminished fMLP-induced L-selectin shedding, and an impaired oxidative burst after cytokine priming. 752 41

We examined the T-lymphocyte phenotypes of 67 human immunodeficiency virus (HIV)-infected children (P-1 or P-2) and 65 age-matched, healthy, control children stratified into four groups from < 1 to > or = 5 years of age to determine expression of antigens associated with cell activation/differentiation. Immunophenotyping was performed by laser flow cytometry using two-color immunofluorescent labeling. Although the control children showed a decline in total CD4 cell percent with age, the HIV-infected children in all age groups showed significantly decreased CD4 cell numbers compared with the age-matched controls. However, the slope of the CD4 cell decline with age was not significantly different in HIV-infected and control children. The CD4 cell decrease in infected children was reflected in both the CD45RA+ (naive) and CD45RA- (memory) CD4 cell subsets, although the CD45RA+ cells were decreased in greater proportion. Results assessing CD4 cells for expression of the L-selectin (Leu8) molecule were similar to those for CD45RA. The overall CD8 cell percentage was significantly increased in HIV-infected children compared with controls in all age groups. This was due primarily to increases in CD8 cells that were CD38+, CD57+, HLA-DR+, or CD45RA-. In a retrospective analysis of data from 23 P-0 children, we compared phenotype results from 5 children who were HIV+ with those 18 who were HIV-. Although the phenotypic changes seen in the 5 HIV+ children paralleled those described above for P-1 and P-2 subjects, there was no significant difference in the values for HIV+ compared with HIV P-0 children. Although the phenotypic alterations described did not appear to be diagnostic markers in P-0 children, they may serve as useful adjuncts for the evaluation of HIV-infected children.
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PMID:Activation and differentiation antigens on T cells of healthy, at-risk, and HIV-infected children. 768 45

We have previously shown that retinoids can induce differentiation of B cells in vitro as well as in vivo in patients with common variable immunodeficiency (CVI). While changes were observed over 1 week when retinoic acid (RA) was added to CVI hybridoma cells in vitro, maturation of the patients' B-cell compartment in vivo occurred only after 4 months of drug administration. We have now performed a 64-week open trial of oral 13-cis RA in five patients to see if prolonged treatment would result in continued improvement in their humoral immune compartment. In this trial, drug was given for 32 weeks followed by a 32-week wash-out period. During the treatment, the patients showed changes in a variety of parameters indicating an alteration towards normal of their humoral immune systems. This change included a fall in the elevated circulating interleukin-6 (IL-6) levels, a more normal display of B-cell surface markers (L-selectin and CD20), a decrease in B-cell size, and improved in vitro and in vivo B-cell function. In order to determine if VH gene use was affected by the retinoid treatment, VH gene expression in the CVI patients was characterized. Results showed an unusual predominance of non-mutated VH gene sequences, representative of cells that are recent bone marrow emigrants. While no common pattern of change occurred in VH gene segment use in the patients while on retinoid therapy, large-scale (> 10-fold) changes in the expression of these genes were observed in each individual over time. Taken together, these results provide multiple lines of evidence that 13-cis RA promotes maturation of B cells in patients with CVI. However, the effect appears to be partial, such that stimuli in addition to 13-cis RA will be necessary to provide for further B-cell differentiation in order to achieve normalization of humoral immunity.
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PMID:Long-term administration of 13-cis retinoic acid in common variable immunodeficiency: circulating interleukin-6 levels, B-cell surface molecule display, and in vitro and in vivo B-cell antibody production. 828 20

Impaired polymorphonuclear neutrophil (PMN) function may contribute to the onset of certain bacterial and fungal infections and to tissue damage in human immunodeficiency virus (HIV)-infected patients. Published data on PMN function in HIV infection are controversial, possibly because most studies have involved PMNs isolated from the normal blood environment by various procedures that may modify PMN responses. We therefore used flow cytometry to study the expression of adhesion molecules at the PMN surface, actin polymerization, and the oxidative burst of whole-blood PMNs in 42 HIV-infected patients at different stages of the disease. These PMNs were activated in vivo, as shown by increased expression of the adhesion molecule CD11b/CD18, reduced L-selectin antigen expression, increased actin polymerization, and increased H2O2 production. The alterations were present in asymptomatic patients with CD4+ cell counts above 500/microliters and did not increase with progression of the disease. This PMN activation could contribute to the oxidative stress described in HIV infection. Stimulation by bacterial N-formyl peptides showed dysregulation of L-selectin shedding and decreased H2O2 production after cx vivo priming with tumor necrosis factor-alpha or interleukin-8. These latter impairments, which correlated with the decrease in CD4+ lymphocyte numbers, could contribute to the increased susceptibility of HIV-infected patients to bacterial infections.
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PMID:Impairment of polymorphonuclear neutrophil function in HIV-infected patients. 869 65

In vivo infection with human immunodeficiency virus type 1 (HIV-1) leads to gradual depletion of CD4+ T lymphocytes from the peripheral blood and later from the lymphoid organs. The mechanism of CD4 cell depletion is not known. HIV can only replicate in dividing lymphocytes, but greater than 98% of the lymphocytes in vivo at any given time are resting and are not permissive for productive infection. We found that exposure of resting CD4+ T lymphocytes to HIV-1 transiently upregulated expression of cell surface CD62L (L-selectin), the receptor for homing to lymph nodes, with concomitant enhanced ability of these cells to bind to lymph node high endothelial venules in an ex vivo homing assay (increased approximately 12-fold, P < 0.001) and to home from the blood into lymph nodes following intravenous injection into SCID mice. This suggested the possibility that decreases in numbers of CD4+ T lymphocytes in the blood of HIV-1-infected subjects may reflect enhanced homing of abortively infected, resting lymphocytes into lymph nodes rather than direct virus replication in and killing of these cells, and may explain development of lymphadenopathy at a time when numbers of CD4+ T lymphocytes in the blood fall.
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PMID:HIV induces homing of resting T lymphocytes to lymph nodes. 912 20

The acute stage of feline immunodeficiency virus (FIV) infection is characterized by the appearance of a major CD8 subpopulation with reduced expression of the CD8 beta chain (CD8alpha+betalo). CD8 antiviral activity was subsequently shown to be mediated by the CD8alpha+betalo phenotype, which is the dominant CD8 phenotype in long-term infected cats. Two- and three-color flow cytometric analysis demonstrated that the CD8alpha+betalo subset is L-selectin negative (CD62L-) and has increased expression of CD44, CD49d, and CD18, consistent with an activation phenotype. The CD8alpha+betaloCD62L- cells but not the CD8alpha+betahiCD62L+ cells demonstrated strong antiviral activity in the FIV acute-infection assay. The progressive expansion of the CD8alpha+betaloCD62L- effector subset cells in FIV-infected cats parallels that seen in human immunodeficiency virus (HIV)-infected patients, suggesting that failure in homeostatic mechanisms regulating lymphocyte activation or trafficking (or both) may be a consequence of both HIV and FIV infections.
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PMID:Progressive expansion of an L-selectin-negative CD8 cell with anti-feline immunodeficiency virus (FIV) suppressor function in the circulation of FIV-infected cats. 1051 9

The Rho GTPase, Rac2, is expressed only in hematopoietic cell lineages, suggesting a specific cellular function in these cells. Genetic targeting studies in mice showed that Rac2 is an essential regulator of neutrophil chemotaxis, L-selectin capture and rolling, and superoxide production. Recently, a dominant negative mutation of Rac2, D57N, has been reported to be associated with a human phagocytic immunodeficiency. To understand further the cellular phenotypes associated with this D57N Rac2 mutant we examined its biochemical characteristics and functional effects when expressed in primary murine bone marrow cells. When compared with wild type (WT) Rac2, D57N Rac2 displayed approximately 10% GTP binding ability resulting from a markedly enhanced rate of GTP dissociation and did not respond to the guanine nucleotide exchange factors. These results suggest that D57N Rac2 may act in a dominant negative fashion in cells by sequestering endogenous guanine nucleotide exchange factors. When expressed in hematopoietic cells, D57N Rac2 reduced endogenous activities of not only Rac2, but also Rac1 and decreased cell expansion in vitro in the presence of growth factors due to increased cell apoptosis. Unexpectedly, D57N expression had no effect on proliferation. In contrast, expansion of cells transduced with WT Rac2 and a dominant active mutant, Q61L, was associated with significantly increased proliferation. Transplantation of transduced bone marrow cells into lethally irradiated recipients showed that the percentage of D57N-containing peripheral blood cells decreased markedly from 40% at 1 month to <5% by 3 months postinjection. Neutrophils derived in vitro from the transduced progenitor cells containing D57N demonstrated markedly impaired migration and O(2)(-) responses to formyl-methionyl-leucyl-phenylalanine, reflecting the same cellular phenotype in these differentiated cells as those described previously in patient cells. These data suggest that the phenotypic abnormalities associated with D57N Rac2 may involve not only neutrophil cellular functions, but also abnormal cell survival in other hematopoietic cells and that overexpression of Rac leads to increased proliferation of normal cells in vitro, whereas deficiency of Rac leads to increased apoptosis.
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PMID:Biochemical and biological characterization of a human Rac2 GTPase mutant associated with phagocytic immunodeficiency. 1127 78

Ovine lentivirus (OvLV) belongs to the family Retroviridae and closely resembles the human immunodeficiency virus (HIV). Pulmonary lesions in OvLV-infected sheep consist of lymphoid interstitial pneumonia (LIP) and lymphocytic alveolitis. Similar pulmonary lesions occur in up to 40% of HIV-infected children and in some adults with AIDS. Interferon-tau (IFN-tau), a type I IFN, is produced by trophectoderm of ruminant conceptuses and is the pregnancy recognition signal in these species. To evaluate changes in phenotypes of bronchoalveolar lavage (BAL) cells of OvLV-infected lambs treated with recombinant ovine IFN-tau (rOvIFN-tau), 24 lambs were randomly allocated to one of four groups (n = 6 per group): 1, no virus + placebo (NVP); 2, no virus + rOvIFN-tau (NVI); 3, virus + placebo (VP); 4, virus + rOvIFN-tau (VI). The BAL cells from 3 lambs in each group were labeled with monoclonal antibodies (mAb) to cell surface markers at 16 weeks of treatment, and cells from the remaining 3 lambs in each group were labeled with mAb at 34 weeks of treatment. After labeling, BAL cells were analyzed by flow cytometry. The morphology of BAL cells from all experimental lambs was examined by transmission electron microscopy (TEM). At week 16, no differences in the relative proportions of BAL cell phenotypes were detected among the experimental groups. At week 34, VI lambs had higher proportions of CD8(+), gammadelta(+), MHC class II(+), and L-selectin (LS(+)) BAL cells compared with VP lambs. Higher proportions of CD14(+) and CD44(+) cells were found in VP lambs compared with NVP lambs at 34 weeks. OvLV-like particles were detected only in bronchoalveolar macrophages of VP lambs. In this study, rOvIFN-tau increased the proportions of primary antiviral gammadelta(+) and CD8(+) immune cells in OvLV-infected lambs. This may represent a cellular mechanism to explain the antiviral and therapeutic efficacy of this cytokine, in addition to its direct antiviral effect. However, because the actual number of cells labeled with mAb CD8 was low and some subsets of gammadelta cells may coexpress the CD8 marker, further studies are necessary to better define the role of rOvIFN-tau in the modulation of these cells in vivo.
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PMID:Phenotypic and ultrastructural characteristics of bronchoalveolar lavage cells of lentivirus-infected lambs treated with recombinant ovine IFN-tau. 1157 62

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