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

The nonlytic suppression of human immunodeficiency virus (HIV) production from infected CD4+ T cells by CD8+ lymphocytes from HIV-infected individuals is one of the most potent host-mediated antiviral activities observed in vitro. We demonstrate that the pleiotropic cytokine interleukin 2 (IL-2), but not IL-12, is a potent inducer of the CD8+ HIV suppressor phenomenon. IL-2 induces HIV expression in peripheral blood or lymph node mononuclear cells from HIV-infected individuals in the absence of CD8+ T cells. However, IL-2 induces CD8+ T cells to suppress HIV expression when added back to these cultures, and this effect dramatically supersedes the ability to IL-2 to induce HIV expression. Five to 25 times fewer CD8+ cells were required to obtain comparable levels of inhibition of viral production if they were activated in the presence of IL-2 as compared with IL-12 or no exogenous cytokine. Furthermore, IL-2 appeared either to induce a qualitative increase in HIV suppressor cell activity or to increase the relative frequency of suppressor cells in the activated (CD25+) CD8+ populations. Analyses of proviral levels in peripheral blood mononuclear cells suggest that CD8+ T cell-mediated lysis of in vivo infected cells is not induced by IL-2. These results have implications for our understanding of the effects of impaired IL-2 production during HIV disease as well as the overall effects of IL-2-based immunotherapy on HIV replication in vivo.
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PMID:Interleukin 2 induces CD8+ T cell-mediated suppression of human immunodeficiency virus replication in CD4+ T cells and this effect overrides its ability to stimulate virus expression. 747 22

Infection with the human immunodeficiency virus type 1 (HIV-1) requires T-cell activation. Recent studies have shown that interactions of the T-lymphocyte receptors CD28 and CTLA-4 with their counter receptor, B7, on antigen-presenting cells are required for optimal T-cell activation. Here we show that HIV-1 infection is associated with decreased expression of CD28 and increased expression of B7 on CD4+ T-cell lines generated from seropositive donors by alloantigen stimulation. Loss of CD28 expression was not seen on CD4+ T-cell lines from seronegative donors, but up-regulation of B7 expression was observed upon more prolonged culture. Both T-cell proliferation and interleukin 2 mRNA accumulation in HIV-1-infected cultures required costimulation with exogenous B7 because these events were blocked by CTLA4Ig, a soluble form of CTLA-4 that binds B7 with high avidity. In contrast, levels of HIV-1 RNA were not affected by CTLA4Ig, indicating that regulation of virus transcription in these cultures did not depend upon CD28-B7 engagement. Infected T cells could present alloantigen to fresh, uninfected CD4+ T cells, leading to increased proliferation and virus spread to the activated cells. Both of these events were blocked by CTLA4Ig. Thus, chronic activation of HIV-1-infected CD4+ T cells reduces expression of CD28 and increases expression of B7, thereby enabling these T cells to become antigen-presenting cells for uninfected CD4+ T cells; this might be another mechanism for HIV-1 transmission via T-cell-T-cell contact.
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PMID:Costimulation of T-cell activation and virus production by B7 antigen on activated CD4+ T cells from human immunodeficiency virus type 1-infected donors. 750 94

Papaverine hydrochloride (PAP) has previously been shown to have a potent inhibitory effect on the replication of viruses such as cytomegalovirus (CMV) and measles. In this report the effect of PAP on human immunodeficiency virus (HIV) replication and T lymphocyte cell function were examined. MT4 cells infected with HIV strain 3b were incubated with serial dilutions of PAP (1-30 microM). At selected times postinfection HIV replication was measured by reverse transcriptase activity (RT) or HIV p24 Ag. PAP significantly inhibited HIV replication by more than 99% at doses of 30 microM with an CD50 and ED50 of 32 microM and 5.8 microM respectively. The mechanism of inhibition of HIV caused by PAP appeared independent form its ability to increase intracellular levels of cAMP and was not mediated via a direct effect on RT activity. To examine T cell function, peripheral blood mononuclear cells (PBMC) from normal donors were stimulated with phytohemagglutinin (PHA) or CMV Ag in the presence or absence of PAP (1-30 microM). At selected times proliferative response to PHA and CMV Ag were determined by [3H]thymidine uptake. In addition, interferon (IFN) gamma and interleukin 2 (IL2) response to mitogens were measured by radioimmunoassay (RIA). PAP enhanced PHA induced IFN production at doses of 1-10 microM and CMV Ag induced IFN production at doses of 1-3 microM. Higher doses were inhibitory. PAP did not affect IL-2 production or IL2 receptor expression and had an inhibitory effect on mitogenic responses.
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PMID:Papaverine hydrochloride: effects on HIV replication and T-lymphocyte cell function. 750 1

Flow cytometry has been employed to study NK cell cytotoxic activity in cats infected with feline immunodeficiency virus. The results show that animals infected for 12 months or more have decreased levels of NK cell cytotoxic activity in their blood. The impairment could not be overcome by in vitro treatment of effector cells with interleukin 2. Additional results suggest that the NK cells of infected cats are defective, in that they are still able to bind to target cells but have a reduced ability to kill them.
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PMID:Defective natural killer cell cytotoxic activity in feline immunodeficiency virus-infected cats. 757 35

Although immunodeficiency viruses can enter resting CD4+ T lymphocytes, activation of T cells is required for complete viral cDNA synthesis and transport of double-stranded viral DNA to the nucleus. Cross-linking T cell receptors (TCRs) on resting CD4+ T cells induces reverse transcription of full-length simian immunodeficiency virus (SIV) genomes, but TCR engagement alone is insufficient to stimulate SIV DNA to move to the nucleus and form long terminal repeat (LTR) circles. Neither ligation of TCR or CD28 receptors nor interleukin 2 (IL-2) alone induces formation of LTR circles; however, the combination of TCR ligation with either CD28 ligation or IL-2 doses. Anti-IL-2 serum inhibits the formation of LTR circles induced by cross-linking CD3 and CD28, but has no effect on the induction of increased viral reverse transcription. Thus, two signals appear to be required for immunodeficiency viruses to move to the T cell nucleus, one from the TCR to promote reverse transcription of the viral genome, the other through an IL-2-dependent process leading to formation of LTR circles.
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PMID:Formation of simian immunodeficiency virus long terminal repeat circles in resting T cells requires both T cell receptor- and IL-2-dependent activation. 762 19

Virus-specific cytotoxic T lymphocytes (CTL) may be an important host defense mechanism in the control of virus replication in persons infected with human immunodeficiency virus type 1 (HIV-1). Cytotoxic T-cell lines generated by nonspecific stimulation with anti-CD3 monoclonal antibodies and interleukin 2 were used to identify regions within the HIV-1 Gag protein that are the most frequently recognized. Using autologous Epstein-Barr virus-transformed target cells infected with recombinant vaccinia viruses encoding p18gag, p24gag, and p55gag proteins of HIV-1/Lai or selected truncations of p24gag, we show that within a group of 29 infected subjects, the p24gag protein is the target of Gag-specific CTL in most donors. Using autologous Epstein-Barr virus-transformed target cells coated with different synthetic peptides spanning the Gag amino acid sequence, we found clusters of partially overlapping peptides in three conserved regions of the p24 protein (amino acids [aa] 169 to 192, aa 219 to 304, and aa 335 to 372) that are frequently recognized by CTL and presented by a variety of human leukocyte antigen class I molecules. Since there are experiments both in vitro and in vivo showing the role of CTL in the control of virus replication in HIV and simian immunodeficiency virus infections, these results may be particularly important for vaccine development.
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PMID:Gag-specific cytotoxic T lymphocytes from human immunodeficiency virus type 1-infected individuals: Gag epitopes are clustered in three regions of the p24gag protein. 767 3

The cause of the profound immunodeficiency state induced by the human immunodeficiency virus (HIV) is not yet fully understood. Although direct cytopathic effects of the virus leading to the loss of CD4+ lymphocytes are believed to play a major role, soluble factors that cause lymphocyte dysfunction have also been identified. Here, we demonstrate that sera of AIDS patients contain a viral component capable of profoundly inhibiting normal T lymphocyte and natural killer cell functions. This factor (M(r) 30,000-50,000) is relatively resistant to proteolytic degradation, heat denaturation, extreme pH, and chemical modifications. It has been determined by Western blotting to share epitopes with the gp41 viral transmembrane component of HIV-1. This immunosuppressive factor has the characteristic property of inhibiting lymphocyte activation in the early stage (within 3 hr) of mitogenic stimulation. Concomitant with the inhibition of lymphocyte activation and interleukin 2 (IL-2) production, transcription of the IL-2 message is also reduced in a time-dependent manner. The unique time dependency of this immunosuppressive factor in lymphocyte activation could serve as a valuable tool to study the early steps of signal transduction in lymphocyte activation beyond membrane interaction.
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PMID:Partial purification and identification of an immunosuppressive factor in AIDS sera. 768 13

A decrease in natural killer (NK) cell function has been related to the progression of human immunodeficiency virus (HIV) infection. In the present study, we assessed the ability of a streptococcus-derived biologic response modifier, OK-432, to augment NK lysis of uninfected K562 and U937 cells and HIV-infected U937 cells by peripheral blood mononuclear cells (PBMC) from HIV-seropositive homosexual men. Optimal two- to fourfold increases in lysis of the three targets were observed after pretreatment of PBMC from HIV-negative subjects for 4 h with 2 micrograms of OK-432 per ml. This effect was related primarily to gamma interferon (IFN-gamma) production induced by OK-432 and was not linked to production of tumor necrosis factors alpha and beta or to monocytes in the cultures. The enhancing effect of OK-432 on NK cell function was diminished but still evident in PBMC from subjects with relatively early-phase (< 3-year) HIV infection and high CD4+ cell counts and was lower in subjects with longer-term HIV infection (> 3 years), in association with reduced production of IFN-gamma. Augmentation of NK cell activity in HIV-infected men by OK-432 was comparable to that induced by treatment of cells with 1,000 U of IFN-alpha or interleukin 2 per ml. The data suggest that the NK cell-enhancing effects of OK-432 are at least in part mediated by IFN-gamma and that OK-432 may be effective in treatment of patients with early-phase HIV infection.
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PMID:Enhancement of natural killer cell activity in human immunodeficiency virus-infected subjects by in vitro treatment with biologic response modifier OK-432. 771 19

Analogs of the immunosuppressive cyclic undecapeptide cyclosporin A (CsA) with substitutions in positions 1, 4, 6, and/or 11 were rationally designed to possess substantially diminished or no immunosuppressive activity. When these compounds were assayed for their capacity to interfere with the replication of human immunodeficiency virus, some displayed a potent antiviral activity in newly infected cells. However, only CsA could interfere with virus replication in persistently infected cells. One CsA analog with antiviral activity costimulated the phytohemagglutinin-induced production of interleukin 2 by human lymphocytes. Human immunodeficiency virus particles from drug-exposed cells showed lower infectivity than virions from untreated cells. Thus, these nonimmunosuppressive analogs of CsA constitute a promising class of lead compounds to develop drugs for effective treatment of the acquired immunodeficiency syndrome.
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PMID:Inhibition of human immunodeficiency virus replication by nonimmunosuppressive analogs of cyclosporin A. 777 16

Cytokines are potent factors mediating interactions between the immune and nervous systems. Cytokines released by macrophages/microglia, the predominant immune cell within the brain, have been proposed to modulate neuronal survival and death. In human immunodeficiency virus-encephalitis (HIVE), cytokines could modulate neurologic damage if nervous system cells possessed appropriate receptors. We hypothesized that the populations of neurons vulnerable to the toxic effects of cytokines in HIVE might contain specific receptors for these molecules. We examined the distribution of cytokine receptors in the human brain utilizing fluorescent-labeled cytokines combined with confocal laser microscopy imaging. Phycoerythrin-conjugated interleukin-1 beta and phycoerythrin-Avidin/biotin conjugated transforming growth factor beta 1 labeled dendritic processes of neurons in the neocortex. Labeling was abolished by pre-incubation with unlabeled cytokines. In cases with moderate HIVE, an average 35% increase in intensity of labeling was observed compared to cases without HIVE or with cases with severe HIVE. The patterns of interleukin 2 labeling were not altered in HIVE. These results suggest that neurons susceptible to cytokine-mediated damage during the progression of HIVE display abnormal patterns of cytokine receptor labeling.
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PMID:Cytokine receptor alterations during HIV infection in the human central nervous system. 785 Apr 58


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