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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T-cell mediated and humoral responses directed to microbial antigens were investigated, at the time of the initial visit, in a group of 139 patients with HIV-1-related persistent generalized lymphadenopathy (PGL) enrolled in a longitudinal study. In vivo and in vitro cell-mediated responses to tuberculin were lower in patients than in controls. Differences were not significant for candidin and streptococcal antigen in vitro, whereas higher responses were observed in the patient group for cytomegalovirus antigen. Following immunization, a subgroup of patients did not have a significantly raised serum antitetanus antibody level, whereas in vitro lymphocyte proliferative responses to tetanus toxoid were lower than in controls. No association was found between these abnormalities and other immunological parameters, including the blood level of CD4+ lymphocytes. Lower responses to most microbial antigens were observed in patients with HIV-1-related symptoms in addition to lymphadenopathy, or the patients who progressed to AIDS in the 2 years following the study. Moreover, intravenous drug users showed higher responses than homosexual patients, possibly because of the influence of previous infections on immunological responses to microbial antigens.
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PMID:Impaired T-lymphocyte-dependent immune responses to microbial antigens in patients with HIV-1-associated persistent generalized lymphadenopathy. 290 65

Persistent, generalized lymphadenopathy (PGL) is a recognized component of human immunodeficiency virus (HIV) infection. We conducted longitudinal studies of B and T cell function in seven homosexual men with HIV infection and PGL. All seven had abnormal antibody-mediated immunity as studied by sequential assessment of in vivo antibody responses after immunization with the T-dependent neoantigens bacteriophage phi X 174 and keyhole limpet hemocyanin (KLH), the T-independent tetradecavalent pneumococcal polysaccharide vaccine, and the recall antigens diphtheria and tetanus toxoid. Compared to HIV-negative heterosexual controls, PGL patients responded with lower antibody titers and, following immunization with phage, failed to develop immunologic memory and to switch from IgM- to IgG-isotype antibody. In vitro antigen-induced antibody production was markedly diminished; and some patients showed depressed mitogen responses. There was a correlation between the degree of compromised immunity and the clinical condition; those with the most severe symptoms showed the most extensive immune deficiency. Yet despite obvious immunologic impairment five of the seven men have remained clinically stable over a 3-year follow-up period.
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PMID:Abnormal antibody responses in patients with persistent generalized lymphadenopathy. 296 10

Ten homosexual men received oral lithium carbonate at doses that maintained their serum lithium concentrations between 0.5 and 1.5 mEq/L. Prior to treatment all patients had HIV isolated from PHA-activated peripheral blood lymphocytes (PBLs) using a quantitative antigen-capture enzyme-linked immunosorbent assay (ELISA) assay for detection, and had an absolute number of CD4 (helper) lymphocytes of less than 300/mm3. Eight of 10 patients developed symptoms of drug toxicity requiring discontinuation of the drug in 7 patients. Two patients completed only 4-5 weeks of lithium therapy, and 5 patients received 7-8 weeks. All patients remained culture positive for HIV during the trial, and viral titers as measured by the antigen capture assay were unchanged or increased. There were no significant changes in the absolute number of CD4 lymphocytes, CD4/CD8 ratio, or phytohemagglutinin (PHA) or tetanus toxoid induced proliferative responses. There was a significant decrease in mixed lymphocyte reaction (MLR). Lithium carbonate demonstrated no immunorestorative or antiviral activity when given in therapeutic doses. Drug toxicity limited therapy in the majority of patients.
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PMID:Effect of lithium carbonate in HIV-infected patients with immune dysfunction. 297 32

We performed a prospective study of 50 subjects at high risk for human immunodeficiency virus (HIV) infection to determine if assays of antigen-specific T cell function provide an earlier indication of future progression to AIDS or a better assessment of immune function than do current methods of evaluation. We measured in vitro T cell responses to Cryptococcus neoformans and tetanus toxoid, response to mitogens, HIV p24 antigenemia, and clinical parameters. Progression to AIDS was significantly associated with loss of T cell response to cryptococci (P = .015), HIV antigenemia (P = .001), and low CD4+ cell numbers (P = .001). Most importantly, we found that loss of antigen-specific responses to cryptococci and tetanus can occur before changes in CD4 cell number. Abnormal response to mitogens and marked depletion of CD4+ cells were late signs of progressive HIV infection. Measurement of antigen-specific T cell function may be useful for assessing the efficacy of antiviral therapy in HIV infection before onset of symptoms.
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PMID:Functional versus phenotypic analysis of T cells in subjects seropositive for the human immunodeficiency virus: a prospective study of in vitro responses to Cryptococcus neoformans. 305 21

We tested the premise that measurement of interleukin 2 receptor (IL2R) and transferrin receptor (TR) can be used to assess proliferative responses to pokeweed mitogen (PWM) and tetanus toxoid (TT). Our study group consisted of patients with Human Immunodeficiency Virus (HIV) infection, including patients with acquired immunodeficiency syndrome (AIDS, n = 10), AIDS-related complex (n = 14), lymphadenopathy syndrome (n = 7), or homosexual men seropositive for HIV (n = 6). Controls were 40 healthy seronegative blood donors. IL2R and TR expression by stimulated mononuclear cells were assessed using specific monoclonal antibodies and flow cytometry, and results were analyzed using the 3H-thymidine assay for DNA synthesis as a standard for comparisons. For identifying low PWM responses, both the IL2R+ cell percent and the IL2R+ cell number (no.) per lymphocyte trigger region (a relative measure of IL2R+ cell no. per culture) on day 3 (72 h) were sensitive (greater than 90%) and specific (80%); day 3 TR+ cell no. was also sensitive (92%) and specific (100%). For detecting low TT-induced responses, day 7 IL2R+ cell no. proved the most sensitive (100%) and specific (78%) parameter. These findings indicate that cytofluorometric analysis of IL2R and/or TR expression is a reliable method for detecting impaired proliferative responses to PWM and TT in these patients. Such a method offers an attractive alternative to the regulatory and disposal problems associated with radioactivity in the conventional DNA synthesis assay, as well as providing insight to the mechanism(s) responsible for impaired proliferation.
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PMID:Early activation marker expression to detect impaired proliferative responses to pokeweed mitogen and tetanus toxoid: studies in patients with AIDS and related disorders. 310 50

Low circulating CD4 cell numbers and CD4 cell dysfunction are distinguishing features of HIV-mediated disease. The current study delineates the in vivo effects of HIV on distinct functional subsets of CD4 cells in homosexually active men who have been infected with HIV for different lengths of time, and examines the capacity of lymphocytes from these men to proliferate in vitro in response to soluble antigen. Although peripherial blood mononuclear cells from most acquired immune deficiency syndrome (AIDS) patients did not proliferate in response to either tetanus toxoid or Candida albicans, cells from most HIV seropositive men without AIDS, many of whom had been infected for more than 18 mo, responded normally to both. Non-responsiveness in HIV-infected men without AIDS was a late event and was associated with longer duration of infection, lower CD4 cell numbers, and subsequent development of AIDS. A defect in this response was observed in only one of 19 HIV seropositive men whose CD4 levels were greater than 300/mm3, but in eight of 10 with levels less than 300/mm3. The defect could not be attributed to a selective depletion of defined CD4 subpopulations that respond to soluble antigen. Dual-color immunofluorescent flow cytometry indicated that 4B4+, 2H4-, and HB-11- CD4 cells were not lost at a faster rate than other CD4 subsets.
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PMID:Early effects of HIV on CD4 lymphocytes in vivo. 310 71

Immunological parameters previously shown to constitute an increased risk for progression towards AIDS have been observed in clinically asymptomatic individuals considered to be at risk for this syndrome. These parameters include severely decreased numbers of T helper cells (count below 400/mm3 blood for CD4+ cells were detected in 7 our of 33 HIV antibody-positive, asymptomatic homosexuals and in 3 out of 29 HIV antibody-positive, asymptomatic drug abusers) and elevated serum IgA and IgM levels (found in 7 to 30 percent of these subjects). Furthermore, up to 60% of risk group members showed a decreased lymphoproliferative response to tetanus toxoid as compared to only 11% of so-called low responders in the simultaneously tested healthy controls. Finally, the capacity to mount an immune response to viral glycoproteins was found to be impaired in individuals at risk for AIDS, as indicated by a low serum level of antibodies to tick-borne meningoencephalitis virus antigen in recently vaccinated subjects.
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PMID:Identification of individuals at increased risk for AIDS among clinically asymptomatic homosexuals and abusers of intravenous drugs. 313 60

It is not clear whether the accessory function of monocytes from subjects with human immunodeficiency virus (HIV)-related diseases such as acquired immunodeficiency syndrome (AIDS) and persistent generalized lymphadenopathy (PGL) is intact. In this study, the accessory function of monocytes from healthy subjects (n = 9) and subjects with AIDS (n = 4) and PGL (n = 5) was assessed by adding graded numbers of monocytes to lymphocytes stimulated with either tetanus toxoid or phytohemagglutinin. By nonparametric analysis, it was determined that a significantly greater number of monocytes was required for half-maximal responses of lymphocytes from subjects with PGL (for tetanus toxid but not phytohemagglutinin) and from those with AIDS, compared with healthy subjects. To address whether this observed difference was a result of a defect in accessory function of monocytes or a result of altered responsiveness of lymphocytes, a mixing experiment was performed between monocytes and lymphocytes obtained from a patient with PGL but without symptoms and an HLA-D-matched healthy sib. Dysfunction of both monocytes and lymphocytes was evident. Thus, this report provides data that monocytes in HIV infection are defective in accessory function for lymphocyte responses to soluble stimuli. We speculate that such dysfunction of monocytes may contribute to the progressive disturbance of the immune response that occurs during HIV infection.
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PMID:Defective accessory function of monocytes in human immunodeficiency virus-related disease syndromes. 326 Sep 32

We have previously demonstrated that recombinant soluble CD4 protein (rsT4) blocks both HIV-1 infection of CD4 bearing lymphocytes and syncytium formation in vitro. (Recombinant soluble CD4 is designated by rsT4). Hence, we suggested the use of rsT4 in therapy for AIDS or the prevention of HIV-1 infection in individuals with a known risk of exposure. However, concerns arose that rsT4 might be immunosuppressive because of its implicated role in the enhancement of certain lymphocyte activation events through its engagement of MHC class II molecules on target cells. We therefore assessed the effect of recombinant soluble CD4 upon a number of functional and activation parameters of lymphocytes, including cellular proliferation, IL-2 secretion, and cytolytic capability, after antigenic or mitogenic stimulation. We report here that rsT4, at 60-fold over the concentration needed to block acute HIV-1 infection in vitro, does not significantly inhibit the activation of human peripheral blood lymphocytes by either PHA, tetanus toxoid or allogeneic cells. These results indicate that rsT4 will potentially exert minimal immunosuppressive effects in vivo, thus supporting the feasibility of clinical trials of rsT4 in the treatment or prevention of AIDS. In addition, the implications of these results for the interactions between CD4 and MHC class II molecules during lymphocyte activation are discussed.
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PMID:Effect of recombinant soluble CD4 on human peripheral blood lymphocyte responses in vitro. 326 92

Infection of monocyte-macrophages with human immunodeficiency virus may be central to the pathogenesis of the acquired immunodeficiency syndrome. The ability of infected macrophages to prime T cells through IL-1 production was investigated in vitro. Purified human monocytes maintained in suspension culture were infected with strain HIV-DV. Intracellular expression of virus p24 antigen increased from undetectable levels immediately after infection to 13-59% of cells by 10-14 d; infected macrophages remained viable for up to 60 d. Supernatants collected between 14 and 20 d after infection were examined in the murine thymocyte co-mitogenesis assay and demonstrated to contain a potent IL-1 inhibitor, designated contra-IL-1. Contra-IL-1 activity was present in all supernatants examined after 4 d of infection, and peaked coincident with peak p24 antigen expression. Inhibitory activity was not present in uninfected cells. Contra-IL-1 activity eluted after gel filtration with an approximate molecular weight of 9 kD. Inhibitory activity was removed by exposure to heat or acid pH, or by incubation with chymotrypsin or staphylococcal V8 protease. Contra-IL-1 did not inhibit IL-2- or IL-4-dependent proliferation of murine T cell lines. Despite its ability to inhibit IL-1 activity, contra-IL-1 did not interfere with the binding of recombinant IL-1 beta to a fibroblast cell line. Contra-IL-1 inhibited the proliferation of normal peripheral blood mononuclear cells to both concanavalin A and tetanus toxoid; inhibition could be attenuated by the addition of exogenous IL-1. Messenger RNA extracted from infected macrophages was examined by Northern analysis for the presence of message to IL-1 beta. No message was apparent, suggesting that the presence of contra-IL-1 was not obscuring the concomitant release of IL-1. Infected macrophages stimulated with endotoxin generated readily detectable message for IL-1 beta. Spleen macrophages purified from two patients with AIDS complicated by immune thrombocytopenia spontaneously expressed p24 antigen in vitro and released contra-IL-1 activity into the media. Contra-IL-1 may contribute to the immune dysfunction of AIDS.
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PMID:Release of interleukin 1 inhibitory activity (contra-IL-1) by human monocyte-derived macrophages infected with human immunodeficiency virus in vitro and in vivo. 326 91


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