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

Lymphocytotoxic autoimmunity (LA) is ubiquitous in AIDS. Its causes are unknown. We report that significant amino acid sequence similarities exist between the proteins of infectious organisms associated with AIDS and the CD4 protein of T-helper lymphocytes. These included: HIV, cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex viruses (HSV), Varicella Zoster virus (VZV), Escherichia coli, Mycobacteria, Mycoplasmas, Plasmodium, and Staphylococcus. It has been reported previously that HIV proteins have significant similarities with human class II MHC (HLA class II) proteins. Since CD4 and HLA class II proteins are chemically complementary, pairs of homologous antigens will also be complementary. It follows that concurrent infections with CD4 and HLA class II-homologous antigens will result in idiotype-antiidiotype antibody pairs that cannot distinguish 'self' from 'nonself', that acts as lymphocytotoxins, and form circulating immune complexes. Thus, combined HIV-CMV, HIV-EBV, HIV-HBV, HIV-mycoplasma, or other appropriate infectious pairs may suffice to trigger LA in AIDS.
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PMID:CD4 similarity to proteins of infectious agents in AIDS and their role in autoimmunity. 773 8

More than 90% of people with AIDS develop circulating immune complexes (CICs) and lymphocytotoxic antibodies (LCTAs). Animals infected with HIV, however, never display CICs or LCTAs, and remain healthy. Similarly, HIV-infected people who do not develop CICs or LCTAs also do not progress to AIDS. The appearance of CICs and LCTAs is, however, highly prognostic for AIDS and death. Since HIV infection does not, per se, lead to the development of CICs and LCTAs, other causes are likely. One such cause, for which both epidemiologic and experimental evidence exists, is semen. Semen components include sperm, seminal fluid, lymphocytes, and sometimes infectious agents, including HIV, mycoplasmas, and herpes and hepatitis viruses, all of which independently cause immune suppression. Extensive evidence demonstrates sperm (and various viruses) contains many proteins mimicking the CD4 protein of T-helper cells, while HIV, mycoplasmas, and seminal fluid mimic class II MHC proteins of other lymphocytes. We identify a large number of protein sequences that display such mimicry using computer homology searching, and demonstrate experimentally that sperm antibodies specifically precipitate antibodies against class II MHC mimics such as mycoplasmas, which in turn precipitate antibodies to lymphocyte antigens. These data prove that immunologic exposure to sperm and lymphocytes (as may occur in receptive anal intercourse, needle sharing, or blood transfusions) is theoretically capable of initiating lymphocytotoxic autoimmunity. Such autoimmunity may play a significant role in the pathogenesis of AIDS, and will need to be addressed clinically in high risk individuals regardless of HIV status and regardless of the success of anti-HIV prophylaxis and treatment.
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PMID:Semen alloantigens and lymphocytotoxic antibodies in AIDS and ICL. 774 57

Epidemiologically, the Acquired Immune Deficiency Syndrome, AIDS, is transmitted and distributed in the USA and Europe almost entirely in well-defined subsets of populations engaging in, or subjected to, the effects of behaviours which carry high risks of genital and systemic infections. The persons predominantly affected are those engaging in promiscuous homosexual and bisexual activity, regular use of addictive drugs, and their sexual and recreational partners. In such persons and in subsets of populations with corresponding life-styles, the risk of AIDS increases by orders of magnitude. Because of continuity of risk behaviour and of associated indicator infections, the incidence of AIDS over 3-5 year periods is predictable to within 10% of actual totals of registered cases in the USA and UK. Secondary transmission of AIDS beyond these groups is minimal or, in many locations, absent. There is no indication of appreciable spread by heterosexual transmission to the general population. The Human Immunodeficiency Virus, HIV, is transmissible to some extent in general populations, and more so among promiscuous persons. It may cause viraemia, lymphadenopathy and latent infection (HIV disease) in anyone. In persons engaging in risk behaviours which themselves alter or suppress immune responses, it can interact with MHC, antibodies to other organisms and to semen, and other allogenic antigens to initiate a programmed death of CD4 lymphocytes and other defensive cells, as in graft-host rejections. This occurs also in haemophiliacs receiving transfusions of blood products, and is more pronounced in persons with reactive HLA haplotypes. The susceptibility of particular subsets of populations to AIDS is thereby largely explained. But these changes occur in the absence of HIV, and so do Kaposi's sarcoma, lymphadenopathies and opportunistic infections which are regarded as main indicators of AIDS. The hypothesis that HIV-1 can do all this by itself and thereby cause AIDS is falsifiable on biological as well as epidemiological grounds. An alternative hypothesis is proposed, linking the incidence of AIDS to the evolution of contemporary risk behaviour in particular communities and locations in the USA, UK and probably in most of Europe. It does not pretend to explain the reported incidence of AIDS in Africa and other developing regions where data are insufficient to provide validation of the pattern of disease and contributory variables. The immediate, practical implication of this alternative hypothesis is that existing programmes for the control of AIDS are wrongly orientated, extremely wasteful of effort and expenditure, and in some respects harmful.
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PMID:The epidemiology and transmission of AIDS: a hypothesis linking behavioural and biological determinants to time, person and place. 774 60

Previous studies from this laboratory indicated infection of dendritic cells (DC) from peripheral blood of individuals infected with HIV1. Here, further evidence for the infection of peripheral blood DC with HIV1 is presented. Low-density cells (LDC) were prepared from blood mononuclear cells of HIV-infected individuals at different clinical stages of disease. These cells are enriched (10-40%) for MHC class-II-bearing DC, while most of the remaining cells are monocytes, and 2-10% are lymphocytes. A quantitative polymerase chain technique (PCR) was used to estimate the HIV provirus load in LDC and lymphocytes of patients in different disease categories. HIV provirus was detected in every LDC preparation, and for many individuals, particularly CDC stage IV patients, the load was higher in the LDC than in the lymphocyte fraction. These findings suggested that patient DC are infected with HIV. In order to provide confirmatory evidence for this conclusion, PCR was performed on DC that were highly purified from LDC by panning to remove contaminating T, B, natural killer and monocytic cells. High levels of HIV provirus were found in these purified DC. These findings suggest that DC provide a reservoir of HIV and that the consequences of such infection may be relevant to the development of disease.
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PMID:Detection of HIV DNA in peripheral blood dendritic cells of HIV-infected individuals. 780 Sep 42

T cells can recognize the antigen only if it is associated with self MHC molecules on the surface of antigen presenting cells (APC). There are several characteristic parameters defining interaction of MHC molecule with antigenic peptides giving circumstances for specific antigen presentation and an individualized immune response. Here are assessed some size and conformational parameters of the peptides presented by MHC class I molecules-lengths, widths, van der Waals volumes and surfaces-using COSMIC 2.0 software. The peptides derived from HIV gp 160 are obtained from literature and are known to be active and inactive in a cytotoxicity assay. An increased tendency for beta- or beta-like structures and volumes close to those of the MHC binding site are encountered in the case of active peptides.
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PMID:Molecular aspects concerning antigen oligopeptide selection by MHC class I molecules. 782 64

The binding of immunogenic peptides to DR molecules is influenced by residues that point into the peptide-binding groove. The T-cell response toward a peptide complexed to an MHC molecule depends on the presence of a sufficient number of T cells reactive with peptide-MHC complex on the surface of APCs. From 96 overlapping HIV peptides, we have selected 11 that show a significant binding to either DR1, DR103, or both. These two DR molecules are identical except for three amino acids at positions 67, 70, and 71 on the beta chain. Peptide-specific T-cell lines and clones were generated with cells from nonimmunized donors homozygous for DR1 or DR103 by using either individual peptides or peptide pools for the in vitro priming. Three of the peptides induced T-cell-specific proliferative response in both individuals, and these peptides were not among those with highest affinity. Most of the peptides induced strong responses against autologous APCs. This might reflect cross-reactivity between HIV and self-peptides. Definition of peptides that both show promiscuous binding to DR and elicit a strong T-cell response is important for design of efficient synthetic vaccines.
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PMID:Promiscuous and specific binding of HIV peptides to HLA-DR1 and DR103. Impact on T-cell repertoire of nonimmunized individuals. 783 66

Direct DNA inoculation induces immune responses through the delivery of nonreplicating transcription units that drive the synthesis of specific foreign proteins within the inoculated host. These proteins are processed within host cells and through association with relevant MHC antigens that can become the subject of immune surveillance and elicit immune responses against pathogens. Direct introduction of DNA into mice has been reported to be antigenic as demonstrated by the use of this technique to develop immune responses against human growth hormone, influenza proteins, as well as HIV-1 proteins. Most recently the demonstration of the use of this technology to produce anti-HIV-1 immune responses has been reported in nonhuman primates. Accordingly a more detailed analysis of this technology could generate important insight into the generality of this approach for immune therapy or vaccine design. In this article we further our investigation of direct DNA inoculation as a tool for induction of relevant immune responses against HIV-1 in vivo. We demonstrate expression of HIV-1 antigens in the inoculated muscle of animals. Inoculated animals demonstrate significant cytotoxic T cell responses against HIV-1 antigen-expressing targets. Furthermore, using a novel challenge system, we demonstrate that the majority of immunized animals can reject lethal, HIV-1 antigen-expressing cell challenge in an antigen-specific manner. This technology has relevance for the development of immunization strategies against HIV as it provides for specific antigen production in vivo without the use of infectious agents.
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PMID:DNA inoculation induces protective in vivo immune responses against cellular challenge with HIV-1 antigen-expressing cells. 786 31

The cellular immune response to HIV-1 has been well studied but, in many respects, remains incompletely defined. Although CTL specificities against highly conserved HIV-1 determinants as dictated by vaccinia/HIV-1 vector constructs have been described, much less is known regarding patient cellular reactivities against autologous cells infected with HIV-1. One of the main obstacles in characterizing this cellular reactivity has been the absence of a targeting system which accurately represents the HIV infected cell in vivo and is, at the same time, adaptable for in vitro assays. Through the use of two separate strategies aimed at increasing cellular CD4 expression, we were able to infect B-lymphocyte cell lines (BLCLs) with multiple strains of HIV-1. HIV-1-infected BLCLs were recognized by autologous effector cells with cytolytic specificities against env, gag, or pol determinants. In addition, HIV-1-infected BLCLs were capable of eliciting in vitro CTL reactivities directed against env-, gag-, and pol-expressing targets. This cellular reactivity was mediated by CD8+ cells and was MHC Class I restricted, suggesting a classical CTL response. Since multiple antigens are recognized, an HIV-1-infected BLCL is a more natural representation of an in vivo cellular target than other available testing systems and should permit a more representative analysis of CTL responses during infection or following vaccination.
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PMID:Multiple CTL specificities against autologous HIV-1-infected BLCLs. 786 83

The role of histocompatibility antigens in HIV infection has been investigated by several approaches. Thus the haplotype A1B8DR3 that is usually linked to autoimmune disorders seems to be associated with accelerated progression to AIDS. Cross-reactivity between MHC antigens and HIV-1 proteins is evident from alloimmunization experiments in mice and xenoimmunization of monkeys with human cells. Furthermore, recent reports suggest that some individuals with uncommon HLA antigens may be resistant to HIV infection. In addition to expressing cross-reacting antigens with HLA, HIV also exhibits substantial amounts of host beta-2 microglobulin and HLA-DR attached to its surface. Taken together, these data are stimulating new hypotheses relevant for AIDS pathogenesis. Based on alloimmunization, novel approaches have also been proposed in attempts to promote an effective immune response to HIV.
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PMID:HLA antigens and resistance to HIV. 786 88

CD8+ cells from HIV-infected individuals inhibit HIV replication in cultured CD4+ cells by a nonlytic, non-MHC-restricted mechanism. The activity appears to be mediated in part by a soluble antiviral factor (CAF) secreted by the CD8+ cells. In an attempt to identify this factor a large panel of recombinant cytokines was examined for their effect on HIV replication in CD4+ cells. In addition to interferon-alpha and -beta, TNF alpha, TGF beta, and IL-8 reduced virus replication in a dose-dependent fashion. In some cases, the effect of the cytokine was also dependent on the HIV infection assay used to measure it. Antibodies against the inhibitory cytokines, as well as antibodies against TNF beta, IFN-alpha, IFN-beta, IL-4, and IL-6 did not inactivate the antiviral effect of CAF. The data suggest that CAF does not have identity with known antiviral cytokines and therefore CAF may be a novel antiviral factor.
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PMID:Effect of cytokines on HIV replication in CD4+ lymphocytes: lack of identity with the CD8+ cell antiviral factor. 790 3


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