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

There is much interest in developing vaccines against acquired immune deficiency syndrome (AIDS), which is caused by a retrovirus termed human immunodeficiency virus (HIV). Isolates of this virus include human T-lymphotropic virus type III (HTLV-III), lymphadenopathy-associated virus (LAV), and AIDS-associated retrovirus (ARV). Several approaches towards the development of an AIDS vaccine result in the production of antibodies in subprimates. These methods involve the use of: antigens isolated from the AIDS virus; viral antigens expressed by transfected cells or by recombinant vaccinia viruses; and particular synthetic peptides of viral antigens. Because T-cell-mediated immunity (in addition to antibodies) is involved in resistance to diseases and death caused by various enveloped viruses, we sought to determine whether potential AIDS vaccines can induce T-cell responses against the AIDS virus. Here we report that immunization of non-human primates, Macaca fascicularis (macaques), with recombinant vaccinia viruses that express LAV envelope glycoproteins gp41 and gp110 results not only in the production of antibodies against the LAV envelope antigens but also in the generation of T-cells that proliferate and produce the lymphokine interleukin-2 (IL-2), in response to stimulation with purified LAV. We believe this is the first report demonstrating T-cell-mediated immunity to the virus that causes AIDS.
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PMID:T-cell responses to human AIDS virus in macaques immunized with recombinant vaccinia viruses. 309 91

A region of human interleukin-2 (IL-2) which was predicted to be a contact point with its receptor was used to locate a homologous region in the envelope protein of human T-lymphotropic retrovirus (HTLV-III). This homologous six amino acid peptide from the carboxy (C)-terminus of the HTLV-III envelope protein was found to inhibit the biological activity of human IL-2 in a murine spleen cell proliferation assay. When conjugated to a carrier protein, this peptide inhibited the binding of radiolabelled IL-2 to its receptor. The biological activity of the peptide was antagonized by a six amino acid peptide fragment of the IL-2 receptor which was predicted to be the contact point on the receptor that corresponded to the binding region of IL-2. The HTLV-III peptide also inhibited the binding of radiolabelled IL-2 to polyclonal anti-IL-2 antiserum. These data support the previous assignment of contact points between IL-2 and its receptor. They also suggest two possible mechanisms of immunosuppression during acquired immunodeficiency syndrome (AIDS). One involves direct competition of the envelope protein or its fragments with IL-2 for binding to the IL-2 receptor. The other involves antibodies to the envelope protein which crossreact with and neutralize IL-2.
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PMID:The HTLV-III envelope protein contains a hexapeptide homologous to a region of interleukin-2 that binds to the interleukin-2 receptor. 309 12

We investigated the expression of the interleukin-2 (IL-2) receptor on phytohaemagglutin-stimulated peripheral blood lymphocytes from homosexual men with persistent generalized lymphadenopathy, the prodrome of the acquired immune deficiency syndrome. The subjects were positive for antibody against human T-cell lymphotropic virus III. Using two-colour fluorescence flow cytometry, IL-2 receptor expression was determined on both the CD4- and CD8-positive lymphocyte subpopulations. After 48 hr of stimulation, expression of the IL-2 receptor on both T-cell subsets was significantly increased in lymphadenopathy patients as compared to values in heterosexual age-matched controls; this difference was less after 72 hr of stimulation. Results from two AIDS patients were within the normal range. IL-2 production was significantly reduced in both lymphadenopathy and AIDS patients as compared to values in heterosexual controls. We conclude that a defect in IL-2 production is associated with human T-cell lymphotropic virus III infection, but that the expression of the IL-2 receptor on T cells is not greatly affected.
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PMID:Increased interleukin-2 receptor expression after mitogen stimulation on CD4- and CD8-positive lymphocytes and decreased interleukin-2 production in HTLV-III antibody-positive symptomatic individuals. 310 Apr 39

Recombinant human interleukin-2 (rIL-2) was administered to 87 patients with the acquired immune deficiency syndrome (AIDS) to test the hypothesis that this lymphokine would correct the underlying qualitative and quantitative deficiency in cellular immunity. Patients were divided into two groups by the presence or absence of Kaposi's sarcoma and subjects within each of these groups received intravenous rIL-2 three times weekly for eight weeks. Subjects received one of several doses which ranged from 1,000 to 2,000,000 units per square meter body surface area. Toxicity at high doses consisted of flu-like symptoms and hypotension at highest doses. Partial objective tumor regression was observed in three patients with Kaposi's sarcoma. Seventeen patients had progression of disease (new opportunistic infection or increase in Kaposi's sarcoma) during therapy. No improvement in immunologic status was observed. This study does not suggest a role for single-agent rIL-2 therapy of established AIDS but its use in less symptomatic persons or in conjunction with antiretroviral agents such as azidothymidine should be investigated.
AIDS Res Hum Retroviruses 1987
PMID:Therapy of acquired immune deficiency syndrome with recombinant interleukin-2. 311 62

A monoclonal antibody (anti-Tac) that appears to bind the receptor for interleukin-2 (IL-2) was used to quantitate lymphocytes that express IL-2 receptors (IL-2R) in response to phytohemagglutinin (PHA) stimulation. 62 +/- 4% of the cells expressed IL-2R in response to PHA in twelve normal subjects compared to 22 +/- 4% in fourteen patients with acquired immune deficiency syndrome (AIDS) (P less than 0.001) and 50 +/- 6% in six patients with AIDS-related complex (P less than 0.1). There was no effect on IL-2R expression, when lymphocytes from seven controls were incubated with IL-2 (20 mu/ml) or thymosin fraction V (10 mu/ml) for 72 h. However, when the lymphocytes from seven patients with AIDS were incubated with IL-2, the IL-2R rose from 18 +/- 3% to 31 +/- 3% (P less than 0.005) and with a fraction V to 29 +/- 3% (P less than 0.001). In addition, IL-2 augmented the PHA-induced proliferative responses in patients with AIDS-related complex and AIDS and normal controls, whereas thymosin fraction V had no significant effect. Thymosin fraction V also enhanced the IL-2 production of PHA-stimulated mononuclear cells obtained from six patients with AIDS and six normal controls. These results suggest that both IL-2 and thymosin fraction V can modulate in vitro T-cell function in patients with AIDS.
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PMID:In vitro immunomodulatory effects of interleukin-2 and thymosin fraction V in acquired immune deficiency syndrome. 311 57

Recombinant vaccinia viruses have been proposed as live vaccines against a variety of infectious diseases, including AIDS (acquired immune deficiency syndrome). Objections have been concerned primarily with side effects of the vaccinia virus vector itself. Recently it has been shown that inactivation of the vaccinia virus thymidine kinase gene or deletion of certain other non-essential genes is associated with a marked reduction in pathogenicity. Nevertheless, the ability of vaccinia virus to produce a progressive infection in immunodeficient individuals remains a most serious problem. Indeed, an incident of this type in a vaccinated man seropositive for human immunodeficiency virus was recently reported. We have used immunodeficient athymic nude mice to establish a model of disseminated vaccinia virus infection, and to demonstrate a novel approach to virus attenuation which involves insertion of a gene encoding human interleukin-2 into the genome of vaccinia virus vectors.
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PMID:Prevention of vaccinia virus infection in immunodeficient mice by vector-directed IL-2 expression. 311 19

The serum levels of a soluble form of the interleukin-2 receptor (sIL-2R) were investigated in 92 patients with human immunodeficiency virus (HIV) infection, ranging from asymptomatic cases to full-blown AIDS. Increased values were found in 69.5% of cases. The overall mean was significantly higher (p less than 0.001) in HIV-infected patients (mean +/- SD = 709.3 +/- 369.4 U/ml) than in the seronegative risk group controls (383.9 +/- 140.5) and normal controls (256.4 +/- 114.5). No major differences were found among the patient groups (asymptomatic infection, persistent generalized lymphadenopathy, symptomatic infection, and full-blown AIDS). These data suggest that the measurement of serum sIL-2R levels may represent a useful biological tool for evaluating T-cell activation phenomena occurring in HIV infection. Since the soluble interleukin-2 receptor maintains the capacity of binding interleukin-2, the increased levels found in HIV infection may play a contributory role towards the in vitro and in vivo impairment of a number of interleukin-2-dependent functions described in this disease. On clinical grounds, the excess of sIL-2R could help to explain the lack of therapeutic effect and little immunological variations following the in vivo administration of interleukin-2.
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PMID:Increased levels of soluble interleukin-2 receptor in the serum of patients with human immunodeficiency virus infection. 312 89

Interleukin-2 (IL-2) is a chemically defined lymphokine (LK) available as mixed human (LK) preparations, as partially purified lymphoblastoid IL-2, or as recombinant human IL-2. Each has different actions dependent on companion LKs showing synergistic interaction (e.g., IL-1 and gamma-interferon (gamma-IFN]). IL-2 acts to expand activated T cells; to activate natural killer (NK) cells, lymphokine-activated killer (LAK) cells, and cytolytic T cells (CTL); to regulate T-cell ontogeny via actions on prothymocytes and immature T cells; and to induce gamma-IFN and activate tumoricidal macrophages. IL-2 acts via specific cell surface receptors on protein kinase C and cyclic GMP-related mechanisms. While stable, its in vivo half-life is short and its persistence is important for it to induce a response. Toxicities include an influenzia-like syndrome, anemia, eosinophilia, and fluid accumulation. In vivo actions include augmentation of cytotoxic responses at high doses, T-cell adjuvant actions, and T-cell restorative actions at midrange doses and at low doses with companion LKs. Antitumor responses in man and animals occur, but irregularly. They are maximized by the concomitant use of LAK cells, cytoreductive therapy, antisuppressor cell therapy, and regional or persistent administration. IL-2 offers hope for more effective therapy of cancer and a variety of immunodeficiency diseases involving IL-2 defects, including AIDS, viral infections, and autoimmune diseases.
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PMID:Recent advances in the preclinical and clinical immunopharmacology of interleukin-2: emphasis on IL-2 as an immunorestorative agent. 314 Oct 54

The tumor-promoting sesquiterpene lactone, thapsigargin, induced a dose-dependent increase of the cytoplasmic Ca2+ concentration ([ Ca2+]i) in human lymphocytes from a resting level between 100 and 150 nM up to about 1 microM. Half-maximum response was found at about 1 nM of thapsigargin, full response at 100 nM. The effect of thapsigargin on [Ca2+]i exceeded that of phytohaemagglutinin (PHA) which raised [Ca2+]i to maximum 300 nM. In combination with phorbol 12-myristate 13-acetate (PMA), thapsigargin stimulated the proliferation of normal lymphocytes to the same extent as did PHA, whereas the thapsigargin/PMA treatment could not restore the defective proliferation of AIDS lymphocytes in spite of the increased [Ca2+]i. Thapsigargin or PMA added separately had no stimulatory effects on cell proliferation. The thapsigargin/PMA treatment caused an increase in the interleukin-2 (IL-2) production of the lymphocytes, which was much higher than that caused by the PHA treatment, even in AIDS lymphocytes. Moreover, the thapsigargin/PMA treatment stimulated the expression of the IL-2 receptors on both normal and AIDS lymphocytes, similar to the effect of PHA. It is concluded that thapsigargin exerts its effects on lymphocyte proliferation by increasing [Ca2+]i, and that the general defect of AIDS lymphocytes, rather than being ascribed to the initiating signal systems, is associated with later events related to DNA synthesis and proliferation.
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PMID:Effect of thapsigargin on cytoplasmic Ca2+ and proliferation of human lymphocytes in relation to AIDS. 314 23

The production of the T cell lymphokine interleukin-2 (IL-2) was found to impaired in all of seven male patients with AIDS or homosexuals with persistent generalized lymphadenopathy (AIDS related complex, AIDS-RC) whom we studied. Conversely the T cell response to IL-2 was found unimpaired as was the production of the monocyte factor interleukin-1 (IL-1). The response of T cells to IL-1 was found markedly decreased in two of the four patients with AIDS and in two of the three patients with AIDS-RC. Five of six patients had flat curves in autologous mixed lymphocyte cultures with no significant proliferative response throughout 7 days. The exception was a Haitian heterosexual patient with AIDS. Natural killer cell function was decreased in three of four patients with AIDS and two of three patients with AIDS-RC but it augmented normally in the presence of IL-2 in four, including the two who had it normal basally. Responses to pokeweed mitogen were within normal limits in all seven patients despite decreased responses to concanavalin A and phytohaemagglutinin. These findings help pinpoint the defect in AIDS to the T4+ cell, and perhaps even to one of its subpopulations, and suggest a role for IL-2 in the treatment of AIDS.
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PMID:Immunoregulatory circuits in the acquired immune deficiency syndrome and related complex. Production of and response to interleukins 1 and 2, NK function and its enhancement by interleukin-2 and kinetics of the autologous mixed lymphocyte reaction. 315 24


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