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

Immunologic changes in HIV-infected homosexual men without AIDS were studied using flow cytometry and monoclonal antibodies. A decline in CD4 cells occurred after anti-HIV antibodies detectable by ELISA developed. CD4 T-cell levels dropped to an average of 60% of their original level within 12-18 months after seroconversion. Subsequently, CD4 levels remained constant in most HIV seropositive men for several years. However, in men who developed AIDS, there was a rapid fall in the CD4 level during the 2 years prior to development of AIDS. Throughout the course of HIV disease, the total T-cell levels (CD3) remained constant, apparently due to CD8 lymphocytosis. The selective depletion by HIV infection of discrete functional subsets of CD4 cells was examined using 4B4, 2H4, HB-11, and Leu-8 monoclonal antibodies and dual color immunofluorescence. No selective depletion of CD4 subsets was noted using any of these reagents. However, selective activation of subsets of CD8 lymphocytes characterized disease progression. In particular, increases in the number of HLA-DR+, CD38+ (OKT10), and Leu-8- CD8 lymphocytes were associated with a fall in CD4 levels and development of AIDS.
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PMID:T-cell subset alterations in HIV-infected homosexual men: NIAID Multicenter AIDS cohort study. 265 13

Recent data suggest that the pathogenicity of HIV is mediated by the production of metabolised viral components which act as hormones. In particular the replication and maturation of T-lymphocytes, and the cellular interaction of immunocompetent cells and nerve cells are affected. The recognition of HIV by the immune system and consequently also the progression of the disease, is influenced by the HLA-type (DR-1) of the infected person. Replication of HIV may be accelerated by the simultaneous presence of other viruses (i.e. cytomegalovirus). So-called apathogenic, attenuated HIV variants have been described.
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PMID:[The pathogenic effect of human immunodeficiency virus. Molecular biological results]. 265 71

The human immunodeficiency virus type 1 (HIV-1) induces a strong cytotoxic T lymphocyte (CTL) response in humans following infection. HIV-specific CTL can be detected directly in the blood and lungs of infected patients, and can be expanded in vitro by stimulation with autologous HIV-infected lymphoblasts. Furthermore, CTL specific for HIV envelope glycoprotein gp160 have been obtained in mice by immunization with recombinant vaccinia virus (VV) that carry the HIV env gene. In this study, we show that mice also produce strong CTL responses to gag and nef proteins following immunization with VV recombinants, thus providing a convenient model system to study T lymphocyte immunity to defined HIV antigens. To determine the specificity of circulating HIV-immune CTL in humans, a panel of doubly transfected mouse P815 tumor cells was produced which express the human HLA-A2 or HLA-A3 transplantation antigen gene and one HIV-1 gene (env, gag or nef). Using these cells as targets to CTL, we show that HIV-infected humans carry co-existing CTL sub-populations of different specificities. Each subpopulation appears to vary in intensity among different individuals. Surprisingly, CTL specific for regulatory, non-structural nef protein appear to be a major constituent of the human immune response to HIV.
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PMID:Multiple subsets of HIV-specific cytotoxic T lymphocytes in humans and in mice. 267 60

The immune response to HIV in infected humans leads to the production of HIV-specific cytotoxic T lymphocytes (CTL) which circulate in high frequencies. The presence of these CTL and their eventual protective activities have been studied by various laboratories, and correlations have been made with certain immunopathological manifestations of HIV infections. It seems probable that HIV-immune CTL participate in the induction of certain disorders by initiating inflammatory reactions in the lungs, central nervous system and lymph nodes. Various virus antigens recognized by HIV-immune CTL on the surface of the infected cell have been identified, and molecular definition of the epitopes recognized is well under way. Likewise, numerous HLA transplantation antigens that regulate HIV antigen recognition by CTL have been identified. These data are discussed with regard to the eventual development of a vaccine and of functional immunotherapies.
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PMID:Cytotoxic T lymphocytes in HIV-induced disease: implications for therapy and vaccination. 269 42

Because T cell responses are critical for defense against viral infections, a series of synthetic peptides derived from the predicted sequence for HIV-1 proteins gp41, pg120, gag, and viral polymerase were used to test the T cell proliferative response of HIV-1 seropositive individuals. Of HIV-1-infected donors from various clinical categories 90% (27/30) had sensitized cells that proliferated in response to at least one of 21 HIV peptides tested. Cells from HIV seronegative controls did not proliferate (0/9) in response to these HIV peptides. Individuals with fewer clinical manifestations of HIV-1 disease responded to a greater number of peptides (average for asymptomatic seropositives = 8.1 peptides; AIDS patients averaged 2.0). The number of peptides recognized also correlated with absolute number of CD4+ cells, but not with delayed cutaneous hypersensitivity to a (non-HIV) battery of Ag. However, clinical stage at no time correlated with the response to any particular peptide. Response patterns differed considerably among individuals, and some peptides stimulated proliferation in many (48%) HIV-infected donors (peptides gp41-2 and pol-3), whereas another peptide elicited no T cell response in any donor tested (peptide gp120-8). We have also begun to investigate the basis for individual heterogeneity of T lymphocyte proliferative responses of HIV-infected donors to the 21 HIV synthetic peptides. Peptide structure and HLA class II determinants both influenced patterns of lymphocyte responses. Reactivity correlated with peptide size, the presence of alpha and beta secondary structure and lack of reverse turn potential. Hydropathy and charge had no predictive value. Peptides derived from HIV sequences that vary highly among strains tended to be recognized less frequently. HIV-infected lymphocyte donors were HLA typed to examine the influence of the MHC on T lymphocyte proliferation. Analysis of the frequencies of individuals reacting to specific peptides, when compared to the allele frequencies in the population at large, indicated association of some responses to DR alleles. More DR association was observed with peptides that showed "moderate" reactivity than with those that were "highly" reactive. We suggest that highly reactive peptides are capable of forming a structure closer to an "ideal" T cell epitope that can associate with many DR alleles. In contrast, "moderately" reactive determinants have less favorable structures for interaction, are more limited in their ability to interact and therefore show more restriction to specific class II alleles.
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PMID:T cell recognition of HIV synthetic peptides in a natural infection. 278 6

Serum levels of soluble interleukin-2 receptors (sIL-2R) were measured in 105 HIV-seropositive individuals simultaneously with T cell subsets and activated T cells (CD3+ and HLA-DR+). Significantly elevated levels of serum sIL-2R were found (564 +/- 259 U/ml versus 258 +/- 87 U/ml in 70 controls, p less than 0.001), as well as increased numbers of activated T cells (mean numbers, 579/microliters in the patients versus 113/microliters in 26 controls, p less than 0.0001). Correlation analysis did not disclose any significant association between elevated sIL-2R and increased activated T cells, nor with decreased CD4+ lymphocytes. These data suggest that sIL-2R in HIV infection do not emanate from activated T cells and are not linked to CD4+ cell loss.
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PMID:Elevated serum levels of soluble interleukin-2 receptors in HIV infection: no correlation with activated T cells. 278 74

HLA-A, -B, -C, -DR, and -DQ antigens were determined by serology and in cases of severe lymphopenia by RFLP-DNA typing in 51 Caucasians with a diagnosis of AIDS (32 with opportunistic infections and 19 with secondary cancers). In addition, 86 HIV-1 seropositive and 39 HIV-1 seronegative drug abusers and 148 healthy controls were also studied. No significant differences in HLA antigen frequencies were found in comparison of HIV-1 seropositive and HIV-1 seronegative drug abusers with controls, suggesting that HLA polymorphism does not represent a genetic risk for infection with HIV-1. In contrast, a significant increased frequency of B35 (p less than 0.01) and CW4 (p less than 0.01) was observed in both groups of AIDS patients as compared to controls. Moreover, DR2 was increased in frequency in patients with opportunistic infections (p less than 0.01) and DR3 was completely absent in patients with secondary cancers (p less than 0.05). In the latter group, the DR5 frequency was increased, although nonsignificantly. These findings provide strong evidence for the existence of HLA-linked factors of susceptibility and host resistance to AIDS.
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PMID:HLA antigens are risk factors for development of AIDS. 278 69

Sera of 95 mothers and 129 children from Nairobi, Kenya, collected in 1976, and of 466 adults and 193 children of Embu District, Kenya, collected in 1984 and 1985, were analyzed for the presence of human immunodeficiency virus type 1 (HIV-1) antibodies. Although no HIV-1 seropositivity was demonstrated by western blot analysis in both study groups, 7% of Nairobi mothers and 10% of adult females from Embu District had false positive results by enzyme immunoassay (EIA) compared with less than 1% seroreactivity rates observed in adult males and children. False positive results were not due to simian T lymphotropic virus type III (STLV-IIIAGM)/human T lymphotropic virus type IV (HTLV-IV) seropositivity. Sixty-one percent of the HIV-1 EIA reactive sera could not be explained by cytotoxic activity to lymphocytes bearing the HLA-DR4 or HLA-DQw3 phenotype. We conclude that false positive HIV EIA tests are frequently encountered in East Africa. Seroprevalence rates in rural Africa must be interpreted with caution due to the decreased specificity of HIV EIAs.
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PMID:Analysis of false positive HIV-1 serologic testing in Kenya. 284 Feb 37

A variety of clinical syndromes, including AIDS and neurological disorders, may follow as a consequence of infection with the human immunodeficiency virus type 1 (HIV-1). It is not yet clear, however, to what extent the destruction of lymphocytes and neural cells associated with these conditions is caused by adverse immune responses to HIV-1 or how much is due to cytopathic effects of the virus itself. Here we document the existence of HLA-restricted, HIV-1-specific cytotoxic T lymphocytes in the cerebrospinal fluid of two AIDS patients manifesting neurologic disorders. These cytotoxic T lymphocytes showed dual specificity, recognizing target cells coated with purified HIV-1 envelope glycoprotein (gp 120) or inactivated HIV-1 in the context of HLA antigens. Cytotoxic T-cell clones derived from one of the AIDS patients revealed restriction specificities representing both HLA class I and HLA class II antigens. Considerable phenotypic heterogeneity was observed amongst these clones, some expressing conventional combinations of cytotoxic T-cell surface markers, and others displaying unusual phenotypes. The presence of HIV-specific cytotoxic T lymphocytes in AIDS patients, and in particular in their cerebrospinal fluid, suggests that these cytotoxic effectors may participate in the lymphoid cell and/or neurologic damage observed in such patients.
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PMID:Phenotypic heterogeneity of cerebrospinal fluid-derived HIV-specific and HLA-restricted cytotoxic T-cell clones. 284 92

The good news reported at the International Conference on Acquired Immune Deficiency Syndrome (AIDS) held in Paris in June 1986 is that among some high-risk groups, the spread of HIV infection at last shows signs of coming under control. This is true both in male homosexuals in several regions of the US and in recipients of blood transfusions or blood products. The former seem to be responding to intensive educational publicity by changes in lifestyle, specifically by adoption of safer sexual practices; the latter are almost certainly benefiting from effective screening of blood donors and, in the case of hemophiliacs, from heat treatment of factors VIII and IX. The bad news reported has 2 major components: the overall perception of risk as expressed in the prediction that only some 10% of HIV-infected individuals will progress to AIDS now appears to have been too optimistic, and, in fact, cohort studies of initially healthy HIV-seropositive subjects generally show no decline in the rate of accumulation of new symptomatic cases even over followup periods in excess of 4 years; and there is growing anxiety over the role of heterosexual contact in transmission of the vrus. Even if the most optimistic forecasts about the spread of HIV are fulfilled, patients already identified as seropositive constitute a serious clinical problem in virtually every major center of population in the world. At this time it simply is not known how many will get AIDS. There are suggestions that susceptibility to AIDS may have a genetic component linked to alleles of the HLA system, but the strength of any such association has yet to be tested in large-scale surveys. Among the many tests that are claimed to be of special prognostic significance are measurements of the specific cellular response to HIV antigen, antigen-stimulated gamma-interferon production, numbers of circulating lymphocytes bearing a combination of surface markers recognized by "CD8" and "Leu7" monoclonal antibodies, hymphocyte responses to pokeweed mitogen, or antilymphocyte antibodies in serum.
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PMID:Who will get AIDS? 287 33


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