Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subsets of activated CD8+ lymphocytes defined by membrane expression of the activation antigens HLA-DR and CD38 were counted by three-color flow cytometry in homosexual men who subsequently became seropositive for human immunodeficiency virus type 1 (HIV). Profound CD8+ cell activation was seen in all subjects at seroconversion and 6 and 12 months later. The HLA-DR+ CD38+ CD8+ cell population, which has potent direct HIV cytotoxic T cell activity, was markedly elevated at seroconversion in all subjects. In some men, these levels remained elevated throughout the first year of infection. During the next 5 years, these men had stable CD4+ cell levels, whereas the others did not. Long-term survivors (seropositive for 9 years, > 800 CD4+ cells/mm3) also had elevated levels of this subset, despite few other activated CD8+ cells. Thus, selective elevation of HLA-DR+ CD38- CD8+ cells was a marker of subsequent stable HIV disease.
 ...
PMID:CD8+ lymphocyte activation at human immunodeficiency virus type 1 seroconversion: development of HLA-DR+ CD38- CD8+ cells is associated with subsequent stable CD4+ cell levels. The Multicenter AIDS Cohort Study Group. 793 Jul 17

The pathogenesis of drug hypersensitivity in patients with HIV infection is unknown. To study further the nature of hypersensitivity, the histopathological features of morbilliform drug hypersensitivity reactions were examined in a group of HIV-infected patients. Skin sections from 23 HIV-infected subjects with morbilliform drug hypersensitivity reactions were examined by light microscopy, direct immunofluorescence and immunohistochemistry, to determine the nature of the inflammatory infiltrate and the role of immunoglobulin, complement and cytokines. The principal light microscopic findings were spongiosis, hydropic generation of the basal layer, civatte bodies, an epidermal lymphocytic infiltrate (48%), and a perivascular dermal infiltrate of lymphocytes (87%) and macrophages (52%). Two patients had findings consistent with toxic epidermal necrolysis. Immunohistochemistry demonstrated that the lymphocytic infiltrate consisted of CD8+, HLA-DR+ T lymphocytes (some of which also stained for CD38), a marked depletion of epidermal Langerhans cells (90%), and strong cytoplasmic staining of keratinocytes for IL-6 (60%), IL-1 beta (50%), tumour necrosis factor-alpha (TNF-alpha) (45%) and to a lesser degree, interferon-gamma (IFN-gamma) (35%). Immunofluorescence did not demonstrate any significant deposition of immunoglobulin or complement. The histological findings were independent of the responsible drug, the duration of either therapy or the rash, and of peripheral blood CD4+ and CD8+ cell counts. These findings suggest that activated CD8+ lymphocytes and perhaps epidermal production of cytokines are involved in the pathogenesis of cutaneous drug hypersensitivity in HIV-infected patients. The common histological features, regardless of the causative drug, suggest a common pathogenesis.
 ...
PMID:Immunohistological assessment of cutaneous drug hypersensitivity in patients with HIV infection. 805 Jan 75

Using a novel anti-CD26 (or anti-dipeptidyl peptidase IV) monoclonal antibody, we showed that the absolute numbers and the proportions of T4 and T8 cells expressing CD26 were significantly lower in HIV-infected persons than in controls. The absolute number of CD26+ T4 cells decreased according to disease progression, whereas the number of CD26+ T8 cells was low throughout all clinical stages. These trends were similar in CD26 dim and bright positive T-cell subsets. In both controls and HIV-positive subjects, the CD26 bright positive T cells were restricted to the CD45RO+ subset and preferentially co-expressed CD25 but largely lacked HLA-DR and CD38. Recall antigen-responsive cells from seronegative individuals were shown to co-express CD26 and CD45RO. The deficient CD26 expression on T8 cells from HIV-infected subjects could be normally upregulated after in vitro stimulation. In contrast to decreased T-cell-bound CD26, the enzymatic activity of plasma CD26/dipeptidyl peptidase IV was unchanged in HIV-infected patients compared with controls. We conclude that HIV infection leads to a deficient in vivo co-expression of CD26 bright and CD45RO on T cells. We speculate that this deficiency might play a part in the decrease of immunological memory during HIV infection.
 ...
PMID:Decreased expression of the memory marker CD26 on both CD4+ and CD8+ T lymphocytes of HIV-infected subjects. 809 10

Flow cytometry is a powerful tool for the multiparametric evaluation of cell surface phenotype in patients with HIV disease. Many cell surface molecules can be evaluated by three-color flow cytometry and the markers correlated with functional activity. It has recently been recognized in adults that the CD8 cell is an important lymphocyte subset in HIV disease that correlates with disease outcome, but there is little information about CD8 subsets in infants. Therefore, we studied infants born to HIV-infected mothers and those born to uninfected mothers. No significant differences were seen in phenotypic markers of activation (CD38, HLA-DR), maturation (CD45RO, CD45RA), and function (CD28) between uninfected infants born to HIV infected or uninfected mothers. In HIV-infected infants, a substantial increase in CD8+ CD38+ HLA-DR+ expression was seen. In addition, we found that there was a significant increase in the CD8+ CD45RO+ CD45RA- subset which is characteristic of the memory phenotype. Finally, evaluation of CD28 (costimulatory molecule involved in T cell activation), which is expressed on almost all CD8 cells at birth, showed that this population was significantly reduced in infected infants. These studies suggest that three-color flow cytometry is a powerful tool for evaluating phenotypic changes in lymphocyte subsets and enhancing our understanding of the pathobiology of HIV disease.
 ...
PMID:A phenotypic study of CD8+ lymphocyte subsets in infants using three-color flow cytometry. 813 61

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.
 ...
PMID:Circulating HIV-specific CD8+ cytotoxic T cells express CD38 and HLA-DR antigens. 845 74

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.
 ...
PMID:Relationship between infectious cell-associated human immunodeficiency virus type 1 load, T lymphocyte subsets, and stage of infection in homosexual men. 856 14

CD8+CD45RA+ T lymphocytes present two distinct subpopulations expressing the CD11a molecule (LFA-1 alpha chain) with different intensity. CD11adim cells represent the unprimed population within the CD8+CD45RA+ subset, whereas CD11abright cells are activated and may be considered as memory lymphocytes. The aim of this study was to analyze the expression of CD11a and CD18 within the CD8+CD45RA+ population in young HIV-infected individuals at different stages of disease as a marker of activation and of disease progression. Blood cells from 82 HIV-infected individuals and 23 age-matched healthy controls were stained with unconjugated CD11a, CD18, PE-goat F(ab')2 anti-mouse, FITC-CD45RA, and TRI-Color CD8. Quantitative analysis for three-color immunofluorescence was carried out by flow cytometry. HIV+ subjects were subdivided into three groups according to their CD4+ cell number (group A, CD4+ cells > 500/microliters [20 subjects], group B, CD4+ cells between 500 and 200/microliters [36 subjects], and group C, CD4+ lymphocytes < 200/microliters [26 subjects]). We found a significant increase of CD11abright in the CD8+CD45RA+ subpopulation throughout the progression of the disease. The CD11abright percentage of positivity (mean) within the CD8+CD45RA+ subpopulation was 31% in healthy donors, 51% in group A, 52% in group B, and 68% in group C. CD11abright expression was closely related to CD18bright (p < 0.001), but not to CD38. The relative increase of CD11a and CD18 expression in CD8+CD45RA+ T lymphocytes parallels the decrease of CD4+ cells and the progression of disease: an inverse correlation between the percentages of CD4+ cells/microliter and CD8+CD45RA+CD11abright cells (p < 0.001) and a direct correlation between the number of CD4+ lymphocytes per microliter and both the number of CD8+CD45RA+CD11adim cells (p < 0.001) and the number of CD8+CD45RA+CD11abright (p = 0.002) was observed. The relative increase of CD8+CD45RA+CD11abright cells may represent an additional marker for monitoring HIV-induced immunodeficiency.
 ...
PMID:Expansion of CD11abright cells in CD8+CD45RA+ from HIV-infected patients: a new early marker for disease progression? 857 89

This is the first time, to our knowledge, that evidence is presented showing that a polyantigenic immunomodulator (PAI), acting as a biological response modifier, can either induce or suppress HIV expression depending on the viral load of infected PBMC. PAI consists of a mixture of inactivated bacteria with influenza virus vaccine. PBMC from HIV-infected patients (asymptomatic, age 22-36, symptomatic, age 30-59 and pediatric, < 2 years old) were co-cultured with PHA-stimulated PBMC from uninfected individuals in medium containing IL-2 and PAI. Parallel co-cultures were carried out in a PAI-free medium. Cultures were fed with PHA-stimulated PBMC from uninfected donors on a weekly basis. HIV-p24 ag and cytokine profiles (IL-1 beta, IL-2, IL-4, IFN-gamma and TNF-alpha) were determined on supernatants on day 14. Peripheral blood samples from each patient were evaluated at the beginning of the experiment as to total CD3, total CD19, CD3/CD4, CD3/CD8, CD16/CD56, CD8/HLA-DR and CD8/CD38 markers through flow cytometry. PAI was able to induce viral expression (up to 11,881 pg/ml of p24 antigen) in cultures showing a low (less than 16 pg/ml) or no viral titer. In contrast, in those cultures with high viral titer (10(2)-10(5) pg/ml), a substantial reduction on the titer was observed upon exposure to PAI. PAI was able to induce the production of IFN-gamma and TNF-alpha while that of IL-4 and IL-1 beta was reduced. The predominant cell type detected in the blood samples of the studied subjects were CD8+, CD8+/CD38+ or CD8+/HLA-DR+.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Changes in viral expression and cytokine profile induced by a polyantigenic immunomodulator in HIV-infected peripheral blood mononuclear cells. 857 53

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.
 ...
PMID:Similarity of expression of activation markers and CD28 on gamma delta and alpha beta-receptor T cells in HIV infection. 862 Jun 25

In a cross-sectional study of 154 HIV-infected and 33 uninfected healthy adults, we show that characteristic changes in the levels of expression of leukocyte surface antigens occur in the HIV-infected individuals. These changes, which collectively occur on virtually every leukocyte subset, are specific: a particular antigen may increase or decrease on one subset of PBMC but remain constant on another. Furthermore, within any particular subset, the levels of one or more antigens may change, while the levels of other surface antigens on the same cells remain constant. Some of these antigens density changes have been noted before, e.g. increased CD20 on B cells, and increased CD38 and HLA-DR on CD8 T cells. However, the multiparameter flow cytometry methodology used here reveals changes in a substantially larger number of surface markers, some of which are restricted to fine subsets of PBMC, such as naive or memory T cell subsets. For many of these antigens, the change in expression correlates with absolute CD4 counts >500/microl; others differ only in those with counts >100microl. The changes in antigen densities we observed on B and T cells are consistent with the observation of a persistent quasi-activated state of these cells in HIV-infected individuals. Similarly, the altered expression of the signal-transducing molecules CD7 and CD16 that we demonstrated for NK cells may correlate with the functional defects previously demonstrated in NK cells. Thus, measurements of antigen densities such as those demonstrated here may provide surrogate markers for the altered functional capacities of PBMC subsets in HIV-infected individuals, and may thereby provide a much simpler assay for immunocompetence than in vitro functional assays.
 ...
PMID:Changes in antigen densities on leukocyte subsets correlate with progression of HIV disease. 867 84


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>