Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We treated a patient with a combined immunodeficiency and disease pathology resembling GvHD with cyclosporine. This disorder was characterized by exfoliative dermatitis, lymphadenopathy, and lymphocytosis of a novel T-cell phenotype (CD3+ TCR alpha/beta+ CD4- CD8-). The patient's peripheral blood T cells had elevated cytolytic activity and expressed increased levels of IL2R, HLA-DR, and CD45RO. Treatment with CsA resulted in marked clinical improvement, resolution of the lymphocytosis, and reduced cytolytic activity of peripheral blood T cells. T-cell HLA-DR and IL2R expression was reduced by cyclosporine, but CD45RO remained intact on virtually all circulating T cells. CsA also inhibited the cytolytic activity and cytokine production of in vitro cultured TCR alpha/beta+ CD4- CD8- cell lines. Our data suggest that alleviation of the patient's clinical symptoms resulted from cyclosporine-mediated suppression of proliferation, cytotoxicity, and inflammatory cytokine production of TCR alpha/beta+ CD4- CD8- T lymphocytes in vivo. The response of this patient to cyclosporine, which was similar to that seen in true GvHD, provides further evidence that these conditions share common pathogenetic pathways.
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PMID:In vivo and in vitro suppression of T-cell receptor alpha/beta CD4- CD8- T lymphocytes by cyclosporine A. 850 Feb 70

Infection with the human immunodeficiency virus HIV-1 is associated with the expansion of a CD14lowCD16high monocyte subset in peripheral blood. This subset, which represents a minor subpopulation of monocytes in healthy individuals, increases during HIV infection and, in patients with AIDS, may represent up to 40% of the total circulating monocyte cell population. The CD14lowCD16high circulating monocytes co-express MAX.1, p150,95 and HLA-DR which are typical of tissue macrophage markers. These cells also express higher levels of intracellular interleukin (IL)-1 alpha and tumor necrosis factor (TNF)-alpha than the CD14highCD16low monocyte population from the same patients. The CD14lowCD16high cells also express low levels of CD35, CD11a and CD4 in common with normal monocytes. When cultured in vitro, monocytes from HIV-seropositive individuals differentiated within a few hours into an elongated fibroblastoid shape characteristic of migratory cells. Our results suggest that the expansion of the CD14lowCD16high monocyte subset, which produce high amount sof TNF-alpha and IL-1 alpha, may participate in the immune dysfunction observed during HIV infection.
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PMID:CD14lowCD16high: a cytokine-producing monocyte subset which expands during human immunodeficiency virus infection. 856 32

Human subjects were experimentally infected with Haemophilus ducreyi for up to 2 weeks. Bacterial suspensions were delivered into the epidermis and dermis through puncture wounds made by an allergy-testing device. Subjects developed papular lesions that evolved into pustules resembling natural disease. Some papular lesions resolved spontaneously, indicating that host responses may clear infection. Bacteria were shed intermittently from lesions, suggesting that H. ducreyi may be transmissible before ulceration. Host responses to infection consisted primarily of cutaneous infiltrate of polymorphonuclear leukocytes, Langerhans cells, macrophages, and CD4 T cells of alpha beta lineage. Expression of HLA-DR by keratinocytes was associated with the presence of interferon-gamma mRNA in the skin. There was little evidence for humoral or peripheral blood mononuclear cell responses to bacterial antigens. The cutaneous infiltrate of CD4 cells and macrophages provides a mechanism that facilitates transmission of human immunodeficiency virus by H. ducreyi.
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PMID:Haemophilus ducreyi elicits a cutaneous infiltrate of CD4 cells during experimental human infection. 856 1

The relationship between cell-associated infectious human immunodeficiency virus type 1 (HIV) load (infectious units/10(6) peripheral blood mononuclear cells [IUPM]) and phenotypes of CD4+ and CD8+ lymphocytes was studied. IUPM were measured in 242 HIV-infected homosexual men by quantitative microculture and T cell subsets by two-color flow cytometry. In multivariate analysis, IUPM correlated negatively with CD4+ lymphocyte level and with a diagnosis of AIDS and positively with the proportion of CD8+ lymphocytes expressing the activation marker CD38. After adjusting for level of CD4+ lymphocytes, men with AIDS had significantly lower IUPM than those without AIDS. The correlation between IUPM and CD4+ lymphocyte level was largely explained by correlation with level of CD4+ lymphocytes with resting phenotypes (HLA-DR-, CD38-) rather than with those expressing HLA-DR and CD38. Thus, subsets of CD4+ lymphocytes may vary in cell-associated infectious HIV content at different stages of HIV infection.
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PMID:Relationship between infectious cell-associated human immunodeficiency virus type 1 load, T lymphocyte subsets, and stage of infection in homosexual men. 856 14

We semiquantitatively monitored the incorporation of host membrane proteins on different strains of human immunodeficiency virus type 1 (HIV-1) grown in several human CD4+ lymphoid cell lines and in primary mitogen-stimulated peripheral blood mononuclear cells. The relative amounts of virally acquired cell proteins were estimated by the ability of HIV-1 to be captured by magnetic beads coated with monoclonal antibodies. Here we report that, among host surface proteins studied, HLA-DR molecules were the most abundant virion-bound host molecules. We have also found that, in contrast to previous studies, HLA-DP and -DQ isotypes were also present on virus progeny. More importantly, we determined that the relative levels of virally acquired host HLA-DR proteins, as estimated by capture with immunomagnetic beads, greatly differed depending on the virus strain and the producer cell. These observations extend beyond already published results and suggest that the process of incorporation of cellular molecules on newly released virus particles is a phenomenon that relies on both the virus strain and producer cell line. These in vitro observations are of prime importance considering that virus-acquired host molecules have been recently shown to affect the biology of HIV.
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PMID:The amount of host HLA-DR proteins acquired by HIV-1 is virus strain- and cell type-specific. 861 Apr 64

Primary pulmonary hypertension (PPH) may have an autoimmune basis that is influenced by host immunogenetics. The pathogenesis of primary pulmonary hypertension in human immunodeficiency virus (HIV) infection is unclear. The objective of this study was to determine whether patients with PPH and HIV infection have distinctive immunogenetic profiles. Ten racially mixed HIV-infected patients with PPH were typed for human leukocyte antigen (HLA) class II (DRB1, 3, 4, 5 and DQB1) by DNA-PCR sequence-specific oligonucleotide probes. Results were compared with two control groups: 128 HIV-negative Caucasians and a previously reported group of 97 HIV-positive, racially mixed control subjects. In those with PPH, there was a significantly increased frequency of HLA-DR6 (-DRB1*1301/2 subtypes) and of HLA-DR52 (DRB3*0301 subtype). These findings suggest that HIV-associated PPH reflects a host response to HIV-1 determined by one or more HLA-DR alleles located within the major histocompatibility complex. The same HLA-DR6 subtype found at increased frequency in our patients has previously been associated with the development of a CD8 lymphocytic host response to HIV-1, termed diffuse infiltrative lymphocytosis syndrome (DILS), which resembles autoimmune Sjogren's disease and is associated with prolonged survival. Together, these findings suggest that HIV-positive PPH may represent a clinical outcome that has similarities with that resulting from the immunogenetically determined host response present in DILS.
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PMID:Primary pulmonary hypertension in HIV infection: an outcome determined by particular HLA class II alleles. 861 57

During human immunodeficiency virus (HIV) infection, phenotypic analysis of circulating gamma delta+ T cells showed a downregulation of the CD28 surface antigen, as recently demonstrated for CD4+ and CD8+ alpha beta+ T cells. The downregulation of the CD28 molecule predominated on CD8+ gamma delta+ T cells. Moreover, an increased expression of CD38 and/or HLA-DR molecules was found on gamma delta T cells as reported for alpha beta T cells indicating that all categories of circulating T lymphocytes share similar phenotypic abnormalities in HIV-infected patients. These unique changes in the different T-cell subsets might be induced by sustained activation of the immune system or by the rapid turnover of T cells and argue for a global dysregulation of T lymphocytes during HIV infection.
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PMID:Similarity of expression of activation markers and CD28 on gamma delta and alpha beta-receptor T cells in HIV infection. 862 Jun 25

Disparate findings have been reported as to whether human immunodeficiency virus (HIV) affects cytokine production by macrophages (MA). We investigated production of different cytokines and of macrophage inflammatory protein (MIP)-1alpha by HIV-1Ba-L- or HIV-1Ada-infected blood-derived MA. Relative to controls, only MIP-1alpha levels increased twofold to > 10-fold in supernatants 2 to 3 weeks postinfection (PI), at the time of maximum virus production; levels of the other chemokines (RANTES, interleukin (IL)-8) and cytokines (IL-1alpha, IL-3, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1) investigated were not affected. MIP-1alpha mRNA signal assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) was, however, only occasionally greater in cells from infected cultures relative to controls. MIP-1alpha levels in supernatants remained in the same range as in control cultures when more than 10 mmol/L Zidovudine was added 24 hours PI, which indicates involvement of virus replication in the effect. Anti-MIP-1alpha antibody labeling identified a 10% to 25% subset of MA, strongly expressing HLA-DR and CD4, and also stained by anti-IL-6 and anti-TNF-alpha antibodies. Two weeks PI, dual staining showed that the majority of the 5% to 20% cells that were p24+ belonged to the MIP-1alpha+ population, which may define a MA subset capable to better sustain HIV replication. MIP-1alpha induced by HIV replication in MA might play a role in the pathophysiology of HIV infection; in impaired hematopoiesis; or as a CD4+ and CD8+ lymphocyte chemoattractant, by recruiting either or both HIV-susceptible and cytotoxic T lymphocytes to virus replication sites.
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PMID:Macrophage inflammatory protein-1alpha is induced by human immunodeficiency virus infection of monocyte-derived macrophages. 863 52

The mechanisms of immune suppression by the human immunodeficiency virus, HIV-1, are more complex than simple helper T cell deletion via infection and viral-induced lysis. Since the recent description of cellular proteins associated with HIV suggests that these proteins may be active in viral pathogenesis, the nature of HLA class II gene product carried on HIV, one of the most abundant of the human components carried with the virus, was examined. HIV bearing HLA-DR was shown to act with bacterial superantigen, staphylococcal enterotoxin A (SEA), to stimulate highly purified human T lymphocytes. T cell stimulation by wild-type HIV was shown by both induction of proliferation and by production of the cytokine interleukin 2 (IL-2). In contrast, HIV produced from mutant cells lacking class II genes were unable to cooperate with SEA to activate T cells. Neither whole HIV nor several proteins purified from HIV (gp120, gp41, p24, p7, and p6) exhibited superantigen-like activity in this system. HLA-DR-bearing HIV could, in the continued presence of SEA, induce T cell apoptosis, as detected by nuclear fragmentation and morphological criteria. These data indicate that human cellular proteins associated with HIV may be biologically active, and these proteins should be considered in mechanisms of viral pathogenicity and immunogenicity.
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PMID:HLA class II on HIV particles is functional in superantigen presentation to human T cells: implications for HIV pathogenesis. 867 86


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