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

Mycobacterium-avium complex (MAC) is an intracellular pathogen and the most common cause of widely disseminated bacterial infection in patients with the acquired immunodeficiency syndrome (AIDS). MAC is infrequently seen in other immunocompromised adults, suggesting that the host defense defect allowing for MAC infection is relatively unique for AIDS. A system was developed for studying the immune response to MAC infection, utilizing MAC isolated from patients with AIDS and monocytes from normal controls and patients with AIDS. Phagocytosis, superoxide anion (SOA) production, and killing were measured. Monocytes from normal controls and AIDS patients were identical with respect to phagocytosis of MAC. In contrast, baseline SOA production was elevated in monocytes from patients compared to normal monocytes and was minimally augmented in response to either phorbol myristate acetate or MAC. Fourteen-day kinetic studies revealed in patients and controls a biphasic pattern with 50-99% killing of AIDS-derived MAC initially, followed always by a rapid outgrowth of surviving bacilli. Despite a modest enhancement of MAC killing by normal but not patients' monocytes pretreated with either recombinant interferon-gamma or recombinant tumor necrosis factor-alpha, outgrowth of MAC was always observed in both, typically faster in patients than in controls. Even monocytes in the presence of lymphocytes stimulated with interleukin-2 did not demonstrate enhanced MAC killing. In contrast, high-titered anti-MAC immune serum derived from a patient with polymyositis and disseminated MAC significantly enhanced the killing of MAC by monocytes from both AIDS patients and healthy controls and prevented their outgrowth. These findings suggest that the host defense defect allowing for MAC infection appears not to reside in the monocyte and that the in vitro lymphocyte functions examined in this study do not appear to play a major role. What role specific antibody plays in vivo in preventing disseminated MAC is uncertain, but the lack of such antibody may help explain the propensity for AIDS patients to develop systemic infection.
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PMID:Host defense against Mycobacterium-avium complex. 284 66

Mononuclear cells (MNC) derived from peripheral blood (PBMNC) of 23 normal donors and 4 AIDS patients, and from bone marrow (BMMNC) of 15 normal donors were incubated at 37 degrees C in culture medium alone or in the presence of either natural or recombinant human interleukin-2 (IL-2) or recombinant human interferon-gamma (IFN-gamma; 1-1,000 U/ml). The cultured cells were washed on days 1, 4 or 7 and tested for various immune functions in vitro and for cell surface phenotype. IL-2, but not IFN-gamma, was found mitogenic for both PBMNC and BMMNC. The natural killer (NK) activity of both PBMNC and BMMNC was the only function tested that was markedly augmented (over 100-fold compared to medium control) by both lymphokines. Pretreatment of PBMNC with IL-2 at greater than or equal to 10 U/ml profoundly suppressed (up to 90%) various functions, such as mitogenic responses (phytohemmagglutinin, concanavalin A, pokeweed mitogen), allogeneic mixed leukocyte reaction, antibody production and T cell colony formation in agar. In contrast, some BMMNC functions were elevated at low doses of IL-2 and IFN-gamma, and significant suppression of BMMNC was seen only with high doses of IL-2 (greater than or equal to 100 U/ml) and IFN-gamma (1,000 U/ml). IL-2 was by far more effective than IFN-gamma in both the amplification of NK activity and the suppression of most of the other functions. IL-2, but not IFN-gamma, was found to activate/induce suppressor cells and increased the proportion of Leu-2+ (CD8) cells in PBMNC; the suppressive effect was time- and dose-dependent. The IL-2-induced suppression could be diminished by inclusion of anti-IL-2 antibody during the pretreatment phase. Similar suppressive effects were noted in PBMNC from AIDS patients. These findings suggest that: (a) high-dose IL-2 may elicit immunosuppression which can be mediated by nondiscriminative highly cytotoxic cells (i.e. lymphokine-activated killer cells) and/or by noncytotoxic, nonspecific suppressor cells, and (b) that PBMNC respond differently to the lymphokines than do BMMNC.
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PMID:Immunomodulating effects in vitro of interleukin-2 and interferon-gamma on human blood and bone marrow mononuclear cells. 289 98

Mononuclear leukocytes from human immunodeficiency virus (HIV)-seronegative and -seropositive homosexual men lysed HIV-infected U937 cells to a significantly greater degree than uninfected U937 cells. Depletion of cell subsets with monoclonal antibodies and complement indicated that the effector cells were primarily of the CD16+ phenotype. Acid-stable alpha interferon (IFN-alpha) production induced by the HIV-infected cells correlated with, although was not an absolute requisite for, preferential lysis of the infected targets. The activity of these CD16+, natural killer (NK) cells decreased in relation to the duration of HIV infection and the presence of acquired immunodeficiency syndrome. Pretreatment of peripheral blood mononuclear cells from HIV-seronegative subjects, but not HIV-seropositive men, with IFN-alpha or recombinant interleukin-2 enhanced lysis of both uninfected and HIV-infected U937 cells. These results suggest that IFN-alpha-associated, NK-like mechanisms are active in the cytotoxic response against HIV-infected cells and that HIV infection results in an early and progressive depression of such responses. Prospective investigations may be useful in determining the role of this NK cell response in the natural history and pathogenesis of HIV infection and the efficacy of therapeutic modalities.
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PMID:Association of alpha interferon production with natural killer cell lysis of U937 cells infected with human immunodeficiency virus. 291 35

In the context of a clinical phase I/II therapy study with recombinant interleukin-2 (rIL-2), we monitored immunological alterations in four patients with acquired immune deficiency syndrome (AIDS) and three patients with AIDS-related complex (ARC). By determining the surface phenotypes and in vitro functions of peripheral blood mononuclear cells (PBMC) before, during, and after treatment with rIL-2, we observed transient changes in all important leukocyte subpopulations, a minor restoration of immune reactivity in vitro, and an improvement in skin reactivity in vivo. In particular, we found a transient increase in C3b receptor-mediated monocyte activation in ARC patients; no influence of therapy on the otherwise intact LPS-induced interleukin-1 production in vitro; in some patients a transient corrective influence on the high pretherapeutic immunoglobulin secretion of B cells and their nonresponsiveness to pokeweed mitogen; low T-cell responses to soluble antigens and alloantigens, which were partially restored during rIL-2 treatment in ARC patients and in one AIDS patient; defective NK activity in PBMC of two AIDS patients, which was found to be restored when measured at the end of rIL-2 therapy; and a rather constant phenotypic pattern of PBMC in each patient during therapy except for the decreasing proportion of OKT9-positive lymphocytes in AIDS patients, the increasing proportion of Leu8-Leu3a+ lymphocytes in all patients, and in particular, the transient significant decrease in the Leu7+/OKT3+ ratio, which pretherapeutically was very high in AIDS patients (0.78 +/- 0.21) and high in ARC patients (0.48 +/- 0.06) as compared to healthy controls (0.18 +/- 0.08).
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PMID:Effects of systemic in vivo interleukin-2 (IL-2) reconstitution in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) on phenotypes and functions of peripheral blood mononuclear cells (PBMC). 294 Feb 58

To investigate if serial measurement of T helper (CD4) lymphocyte number in peripheral blood is of prognostic value, we determined lymphocyte function in asymptomatic and symptomatic HIV antibody positive and negative homosexual males and related the results to absolute number of CD4 lymphocytes in peripheral blood. Lymphocyte function was determined by measuring streptolysin O (SLO)-induced proliferative responses of peripheral blood lymphocytes (PBL) and of PBL depleted of CD8 lymphocytes. Phytohemagglutinin (PHA) induced interleukin-2 (IL-2) production was also measured. In all functional tests values were significantly lower in HIV antibody-positive subjects than in HIV antibody-negative subjects. Results lower than the 95% confidence limit in HIV antibody-negative individuals were therefore defined as "decreased." Decreased functional responses were most frequent (83-100%) in individuals with a number of CD4 lymphocytes of less than 400/microliters, and were least frequent (3-21%) in subjects with a CD4 lymphocyte count of greater than 600/microliters. Frequency of decreased functional responses was intermediate in the population with 600-400/microliters CD4 lymphocytes. The magnitude of functional responses differed significantly between groups with less than 400, 400-600, and greater than 600 CD4 lymphocytes per microliter, indicating that T helper cell number decreases with loss of immune function.
AIDS Res Hum Retroviruses 1988 Aug
PMID:Analysis of absolute T helper cell number and cellular immune defects in HIV antibody positive and negative homosexual men. 297 9

At the end of December 1984, 8246 AIDS cases had been reported in the United States, and 762 cases in Europe. The main risk groups are homosexual and bisexual men (73%), heterosexual i.v. drug addicts (17%) and Haitians (4%). AIDS is diagnosed in patients meeting the clinical criteria of the CDC surveillance definition (opportunistic infections and/or Kaposi's sarcoma). The prevalence of HTLV-III antibodies in risk groups is high, its prognostic significance still controversial. Laboratory methods to determine the more relevant circulating viral proteins or the whole virus are now being developed. Limited studies to evaluate the possibility of reconstituting the immune system of AIDS patients with interleukin-2 and gamma-interferon have proved unsuccessful. successful. Several new drugs with possible antiviral properties are now being evaluated in first clinical trials.
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PMID:[Acquired immunodeficiency syndrome (AIDS). An update after 4 years]. 298 17

14 patients with hemophilia were studied for the distribution of T cell subsets, the presence of antibody to lymphadenopathy-associated or human T lymphotropic virus type III (LAV/HTLV-III), and their responsiveness in autologous mixed lymphocyte reactions. In addition, mitogen and alloantigen responsiveness and Interleukin-2 production were investigated. Seven patients were found to have low Leu 3a/Leu 2a (T4/T8) ratios; eight patients had antibody to LAV/HTLV-III; and an additional patient had acquired immunodeficiency syndrome. Responsiveness to mitogens and alloantigens as well as Interleukin-2 production were comparable with those of healthy individuals. However, patients with low ratio, many of whom had antibodies to LAV/HTLV-III, had a highly deficient autologous mixed lymphocyte reaction. This reduced response of T cells to autologous non-T cells could not be corrected by elimination of Leu 2a/T8 cells, which indicated that there was a preferential loss of the Leu 3a cell subset(s) which responded to autologous non-T cells. Thus, these patients have a deficiency of intercellular communication within their immune system.
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PMID:Deficiency of the autologous mixed lymphocyte reaction in patients with classic hemophilia treated with commercial factor VIII concentrate. Correlation with T cell subset distribution, antibodies to lymphadenopathy-associated or human T lymphotropic virus, and analysis of the cellular basis of the deficiency. 298 34

We studied the effects of sera from patients with the acquired immunodeficiency syndrome (AIDS) on interleukin-2 (IL-2) production to help elucidate the mechanism of immunodeficiency. Compared with sera from healthy controls, sera from AIDS patients suppressed phytohemagglutinin (PHA)-induced IL-2 production by normal blood mononuclear cells. Sera from homosexual contacts of AIDS patients and from adults with acute cytomegalovirus infection generally lacked this suppressive activity. The effect of the AIDS sera could not be attributed to absence of a stimulatory or nutritive factor, to inactivation of IL-2, to inhibition of the IL-2 assay, nor to increased turnover of IL-2. The suppressive effect of the sera was not mediated by radiosensitive or T8 antigen-bearing suppressor cells or by increased prostaglandin production or decreased interleukin-1 production. The sera acted directly on the groups of cells that produce IL-2, T cells and large granular lymphocytes; suppression occurred at an early, probably pretranslational, stage. When cells were incubated with AIDS sera and then washed, the suppressive effect persisted. The sera did not cause direct or complement-mediated cytotoxic effects on normal mononuclear cells nor did they suppress PHA-induced interferon production, nor proliferation of T lymphoblasts or lymphocyte lines. The suppressive effect was not mediated by interferon, cortisol, immunoglobulin G or M, or immune complexes. The activity was stable at pH 3, pH 10, and 60 degrees C; inactivated at 100 degrees C; and not ether extractable. Because IL-2 plays a central role in the development of many immune responses, the serum factor(s) that inhibits IL-2 production could contribute significantly to the immunodeficiency of AIDS.
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PMID:Sera from patients with the acquired immunodeficiency syndrome inhibit production of interleukin-2 by normal lymphocytes. 298 37

The immune systems of patients with acquired immunodeficiency syndrome are characterized by a profound defect in the number and function of helper/inducer T-lymphocytes, particularly at the level of soluble antigen recognition. Due to this selective yet profound defect in the immune system, these patients are prone to recurrent severe opportunistic infections and Kaposi's sarcoma. While therapies exist for some of these complications of acquired immunodeficiency syndrome, no effective therapies exist for the underlying immune defect of this syndrome. Reviewed here are some of our recent attempts at immune reconstitution in acquired immunodeficiency syndrome, using either whole scale immune reconstitution through the use of lymphocyte transfers and bone marrow transplantation or enhancement of the remaining immune systems with the T-cell-derived lymphokines interleukin-2 or immune gamma-interferon. In addition, recent advances in the therapy of Pneumocystis carinii pneumonia and disseminated cytomegalovirus disease are discussed.
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PMID:Therapeutic approaches to patients with AIDS. 299 Jul 6

Infection of normal peripheral blood T cells by the acquired immune deficiency syndrome (AIDS)-associated retrovirus (ARV) was evaluated in long-term cultures of helper-inducer T cells (T4 cells). Cells that were inoculated with ARV and maintained in medium supplemented with interleukin-2 remained productively infected with this virus for more than 4 months in culture, although they showed no cytopathic effects characteristic of acute ARV infection. The presence of replicating virus was demonstrated by reverse transcriptase activity of culture fluids and by viral antigens and budding particles detected on cells by immunofluorescence and electron microscopy. Virus produced in these cultures remained infectious and could induce cytopathic effects and viral antigens in uninfected lymphoid cells. The finding that normal lymphocytes may be productively infected by an AIDS retrovirus in the absence of cell death suggests that a range of biologic effects may occur after infection in vivo.
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PMID:Persistent noncytopathic infection of normal human T lymphocytes with AIDS-associated retrovirus. 299 22


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