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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This overview summarizes current knowledge on the overall efficacy and potential contribution of antibody-dependent cellular cytotoxicity (ADCC) and lymphokine-activated killer cell (LAK) activities in evoking non-major histocompatibility complex (non-MHC) cytolytic responses to human immunodeficiency virus-1 (HIV-1)-infected targets. High titers of ADCC antibodies to the HIV-1 virion are present in HIV-1-seropositive populations at all stages of disease. These antibodies are broadly reactive with a large number of HIV-1 strains and are predominantly directed against envelope determinants spanning both gp120 and gp41. However, the relative ability of natural killer (NK) effectors, derived from HIV-seropositive individuals, to evoke ADCC responses becomes increasingly impaired with disease progression. HIV-1-seropositive individuals also show marked decreases in both production of and responsiveness to interleukin-2 (IL-2). HIV-1-seropositive individuals generally have the ability to generate ex vivo propagated LAK cells; however, these cytolytic effectors are less effective than their counterparts derived from healthy controls. Increased understanding and control of non-MHC-restricted cytotoxic-responses to HIV, and their induction by lymphokines, may lead to improved treatment strategies for the management of AIDS and related diseases.
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PMID:Role of antibody-dependent cellular cytotoxicity and lymphokine-activated killer cells in AIDS and related diseases. 194 Jun 15

To assess the value of feline immunodeficiency virus (FIV) infection as a model for human immunodeficiency virus (HIV) infection in man, we studied the impairment of certain immunological functions following natural or experimental FIV infection. Proliferative responses of peripheral blood mononuclear cells (PBMC) from symptomatic and asymptomatic cats after naturally or experimentally acquired FIV infection, induced by activation with the mitogens concanavalin A, pokeweed mitogen, or lipopolysaccharide or by stimulation with human interleukin-2 (IL-2), were significantly lower than the proliferative responses found with PBMC from noninfected control cats. Also IL-2 production levels of mitogen-activated PBMC from naturally infected symptomatic cats were significantly reduced. These data confirm that the pathogenesis of FIV infection in the cat, like HIV infection in man, is characterized by a serious malfunction of the immune system.
AIDS Res Hum Retroviruses 1990 Dec
PMID:Feline immunodeficiency virus (FIV) infection in the cat as a model for HIV infection in man: FIV-induced impairment of immune function. 196 59

We evaluated three cellular and five serologic markers that are affected by infection with the human immunodeficiency virus type 1 (HIV-1) for their ability to predict the progression to clinical acquired immunodeficiency syndrome (AIDS). The cellular markers were the number of CD4+ T cells, the number of CD8+ T cells, and the ratio of CD4+ T cells to CD8+ T cells. The serologic markers were the serum levels of neopterin (a product of stimulated macrophages), beta 2-microglobulin, soluble interleukin-2 receptors, IgA, and HIV p24 antigen. We evaluated the usefulness of these measures as markers of the progression to AIDS prospectively, over four years, in a cohort of 395 HIV-seropositive homosexual men who were initially free of AIDS. CD4+ T cells (expressed as an absolute number, a percentage of lymphocytes, or a ratio of CD4+ to CD8+ T cells) were the best single predictor of the progression to AIDS, but the serum neopterin and beta 2-microglobulin levels each had nearly as much predictive power. The neopterin level appeared to be a slightly better predictor than the beta 2-microglobulin level. The levels of IgA, interleukin-2 receptors, and p24 antigen had less predictive value. A stepwise multivariate analysis indicated that the best predictors, in descending order, were CD4+ T cells (the percentage of lymphocytes or the CD4+: CD8+ ratio), the serum level of neopterin or beta 2-microglobulin, the level of IgA, that of interleukin-2 receptors, and that of p24 antigen. The last three markers had little additional predictive power beyond that of the first two. We conclude that of the eight markers studied, progression to AIDS was predicted most accurately by the level of CD4+ T cells in combination with the serum level of either neopterin or beta 2-microglobulin. At least one of these two serum markers, which reflect immune activation, should be used along with measurement of CD4+ T cells in disease-classification schemes and in the evaluation of responses to therapy.
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PMID:The prognostic value of cellular and serologic markers in infection with human immunodeficiency virus type 1. 197 15

Rhesus peripheral blood mononuclear cells (PBMC) fail to demonstrate natural killer (NK) activity against the human T-cell lines CEM, CEM x 174, or SUP-T1. However, these cell lines could act as NK-sensitive target cells if they were pulsed with heat-inactivated, whole simian immunodeficiency virus (SIV). The ability of these SIV-pulsed T-cell lines to act as NK-sensitive target cells was directly related to the relative density of CD4 on their surface. Target cell generation was inhibited by preincubation of cell lines with CD4 monoclonal antibody (MAb) with specificity for the SIV binding site. In addition, NK activity was seen against target cells that had been prepared with human immunodeficiency virus type 1 (HIV-1) gp120, nonglycosylated gp120, env A of feline leukemia virus (FeLV), and simian type D retrovirus (SRV). Addition of leupeptin to target cells prior to SIV pulsing did not result in a significant decrease in cytotoxic activity, suggesting that processing is not required for the generation of target cells. The cells that mediate NK activity are nonadherent, do not form rosettes with AET-treated sheep red blood cells (SRBC), and are phenotypically CD16+ and CD8+. NK activity of SIV-infected macaques was significantly decreased against both K562 cells and SIV-pulsed target cells as compared with uninfected animals. However, treatment of PBMC with interleukin-2 (IL-2) resulted in a partial restoration of NK activity.
AIDS Res Hum Retroviruses 1990 Jul
PMID:Natural killer cell activity of rhesus macaques against retrovirus-pulsed CD4+ target cells. 197 94

As condylomata acuminata often persist in individuals infected with the human immunodeficiency virus (HIV), an immunohistological study of warts from infected men was undertaken to further knowledge about human papillomavirus persistence in this group. Using an indirect immunoperoxidase method and a panel of monoclonal antibodies, the phenotypes of cells were studied in cryostat sections of perianal or anal warts removed from 14 HIV-infected men (10 homosexual and 4 heterosexual) and from 16 non-infected men (10 homosexual and 6 heterosexual). Although the median numbers of CD1+, CD3+ and CD4+ cells per unit area were similar in each group of individuals, the number of CD8+ cells was significantly higher in HIV-infected homosexual men when compared with non-infected individuals and HIV-infected heterosexual men. The median CD4+ cell count in the peripheral blood was significantly higher in HIV-infected heterosexual men than in HIV-infected homosexual men (P less than 0.05). These findings may reflect differences in duration of HIV infection between the two groups. There was no significant difference in the proportion of cells expressing interleukin-2 receptors between HIV-infected and non-infected individuals. Natural killer (CD16+) cells were not identified in any of the condylomata.
Int J STD AIDS 1990 Jan
PMID:Immunological study of condylomata acuminata in men infected with the human immunodeficiency virus. 198 71

Lymphokine-activated killer (LAK) activity was analyzed in 31 human immune deficiency virus 1 (HIV-1)-infected patients. It was found to be reduced in all groups of patients, being more pronounced in those with acquired immune deficiency syndrome (AIDS) and AIDS-related complex compared to HIV-1-seropositive, asymptomatic individuals. Only high doses of interleukin-2 were able to restore LAK activity comparable to that of normal controls. In addition, HIV-1 gp41 synthetic peptide sequences 735-752 and 846-860 were able to significantly inhibit normal LAK activity at all the effector:target ratios tested. HIV-1-positive serum and the supernatant fluids from cultured peripheral-blood mononuclear cells from HIV-1-infected patients had the same inhibitory effect on normal LAK activity. These data provide evidence that (1) LAK activity appears to be impaired during the course of HIV-1 infection and (2) HIV-1-positive serum and HIV-1 components could exert a profound inhibition of this functional activity.
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PMID:Inhibition of lymphokine-activated killer activity during HIV infection: role of HIV-1 gp41 synthetic peptides. 208 45

AS101 [ammonium trichloro (dioxyethylene-o-o') tellurate] has been reported to stimulate normal mouse and human lymphoid cells to proliferate and to produce lymphokines such as interleukin-2 (IL-2) and colony-stimulating factor (CSF), regulators of lymphopoiesis and myelopoiesis. In this study, we demonstrate that the IL-2 secretion and cell proliferation of both human and mouse lymphocytes, and the production of CSF by mouse spleen cells, was significantly enhanced by the synergistic effect of AS101 and phorbol myristate acetate (PMA). AS101-induced activation was found to be very sensitive to inhibition by EGTA, the Ca2+ channel blocker, nifedipine, and cyclosporin A (CsA), an agent which selectively suppresses Ca2(+)-activated steps in this process. Our results suggest that AS101 may efficiently trigger the Ca2+ signal required to initiate lymphocyte activation, but that the enhancement observed when cells are stimulated with both AS101 and PMA may be due to the generation of a second signal, probably the activation of protein kinase C (PKC). A more thorough understanding of the mechanism of action of the immunomodulator AS101, presently under clinical trials on cancer and AIDS patients, is highly relevant to the assessment of its optimal application.
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PMID:Synergism between AS101 and PMA in lymphokine production. 210 43

We measured levels of protein, of complement-derived anaphylatoxins (C3a, C4a, and C5a), and of the lymphokines interleukin-2 and gamma interferon, in vitreous humor from 10 AIDS patients with vitritis and retinitis (group 1). We compared these measurements with levels in vitreous from 7 patients with vitritis but without AIDS (group 2), 10 patients with vitreous hemorrhages (group 3), and 20 patients with retinal detachments or epiretinal membranes without clinical evidence of vitreal inflammation (group 4). Vitreous humor from 10 AIDS patients had measurable levels of interleukin-2 in three of nine samples, gamma interferon in six of nine samples, C3a and C4a in all ten samples, and C5a in only one of ten samples. Vitreous humor from group 1 did not differ significantly from vitreous from group 2. On the other hand, vitreous from group 1 had significantly higher levels of gamma interferon, C3a, and C4a, and higher ratios of these anaphylatoxins to protein, in comparison to vitreous in groups 3 and 4. The results of this study suggest that vitreous humor from AIDS patients with retinitis contains activated complement and may contain interleukin-2 and gamma interferon. Viral retinitis is associated with the presence of lymphokines in vitreous humor. Additionally, anaphylatoxin and gamma interferon levels, but not interleukin-2 levels, correlate with vitreal inflammation. This is the first study to measure interleukin-2, gamma interferon, and C5a levels in human vitreous humor.
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PMID:Inflammatory mediators in the vitreous humor of AIDS patients with retinitis. 211 May 58

Viral isolates were recovered by cocultivation on macrophage colony-stimulatingfactor (MCSF)-treated monocyte target cells from peripheral blood mononuclear cells (PBMCs) in 25 out of 27 patients seropositive or at risk for HIV infection. Frequency of virus recovery was independent of the patient's age, sex, numbers of CD4+ T cells, clinical stage or zidovudine (azidothymidine) therapy. Sixteen out of 19 HIV isolates were serially passaged in MCSF- treated monocytes. Five out of five virus isolates were also passaged in phytohemagglutinin/interleukin-2 (PHA/IL-2)-treated lymphoblasts. In lymphoblasts, no qualitative or quantitative differences were observed between these isolates and human T-cell leukemia virus IIIB (HTLV-IIIB) for (1) release of p24 antigen reverse transcriptase, and infectious virus, (2) induction of typical cytopathic effects (cell syncytia in 3-10% of cells) and cell lysis, (3) frequency of infected cells (5-20% of PBMC) as detected by in situ hybridization for HIV RNA, (4) down-modulation of T cell plasma membrane CD4, and (5) site of progeny virion assembly and budding (plasma membrane only with no intracytoplasmic accumulation of virus). Progeny virus recovered from infected lymphoblasts was fully infectious for other lymphoblasts, but failed to infect MCSF-treated monocytes. Detailed analysis of target cell tropism among HIV isolates showed that HIV isolated in monocytes infected both monocytes and lymphoblasts; progeny virus isolated in lymphoblasts infected only T cells. HIV interacts differently with monocytes and T cells. Understanding this interaction may more clearly define both the pathogenesis of HIV disease and strategies for therapeutic intervention.
AIDS 1990 Mar
PMID:Macrophage-HIV interaction: viral isolation and target cell tropism. 211 97

AS101, a synthetic organotellurium compound, was found to have immunomodulating properties by initiation of cytokine production in vitro and in vivo. Phase I/II clinical trials currently in progress on AIDS and cancer patients treated with AS101 show significant increases in various immunological parameters, with minimal toxicity. Recently, AS101 and the protein kinase C (PKC) inducer, phorbol myristate acetate (PMA), were shown to synergize in the secretion of interleukin-2 (IL-2) and colony-stimulating factor (CSF) in vitro, by human and mouse lymphoid cells. The bryostatins, a group of natural macrocyclic lactones isolated from marine invertebrates (Bugula neritina) have been reported to be potent PKC activators with no tumour promoting activity. In this study, we investigated the synergistic effect of AS101 and a partially purified preparation of bryostatin on the production of several cytokines. Our data confirm the presence of synergism, which greatly enhances cell proliferation, IL-2, tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma) secretion by human mononuclear cells (MNC) and the production of IL-2 and TNF by mouse cells. The absence of tumour-promoting activity of the bryostatins makes them particularly good candidates, in combination with AS101, for immunomodulation in vivo in clinically immunosuppressed conditions.
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PMID:Cytokine secretion effected by synergism of the immunomodulator AS101 and the protein kinase C inducer bryostatin. 211 79


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