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

Multinucleated giant cell formation (MNGC) occurs in central nervous system AIDS. The mechanism of fusion of microglia in these cases is unknown. We investigated the ability of lymphokines to induce fusion and found that interleukin-3 (IL-3), interleukin-4 (IL-4), gamma interferon (gamma-IFN), and granulocyte-macrophage colony stimulating factor (GM-CSF) induced MNGC formation in cultures of rat microglia in vitro. The diacylglycerol analogue phorbol myristate acetate (PMA) also induced MNGC. Interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) failed to induce fusion. Preincubation of the IL-3 treated cultures with anti-IL-3, anti-leukocyte function associated antigen-1 (LFA-1) alpha-chain (CD11a), and anti-intercellular adhesion molecule-1 (ICAM-1) inhibited cell fusion. Antibody to polymorphic Class II major histocompatibility complex (MHC) determinants also inhibited MNGCs. Cell surface LFA-1 was predominantly observed on MNGC, suggesting that LFA-1 expression is involved in microglia fusion. We thus propose that MNGC formation of microglia result from the effects of T cell-derived cytokines probably through the induction of cell surface adhesion molecules.
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PMID:Lymphokine induction of rat microglia multinucleated giant cell formation. 850 64

In cell-mediated immunity T cells recognize peptide fragments of the antigenic protein in association with major histocompatibility complex (MHC) proteins. Synthetic 9- to 16-mer peptides have been widely used to identify the region(s) of a protein that act as T cell epitope. Here, we report antigenic peptides identified on HIV-1 regulatory protein Rev. Four synthetic peptides (amino acids 9-23, 25-39, 33-48, and 41-56) were first shown to stimulate T helper (Th) cell proliferation in peripheral blood lymphocytes (PBLs) derived from HIV-seropositive (HIV+) individuals. The same peptides induced cytotoxic T lymphocyte (CTL) activities toward the autologous target cells incubated with the peptides. Both responses were specific to the HIV infection as HIV-seronegative (HIV-) control individuals showed no significant proliferative or cytotoxic activity. The proliferating cells were CD4+ T cells, and CTL activity was mediated by CD8+ human leukocyte antigen (HLA)-restricted T cells. The identification of peptides containing epitopes that can induce both Th and CTL responses to regulatory proteins of HIV-1 in infected individuals might be important for vaccine development against AIDS. Since early regulatory proteins of HIV are expressed by the infected cells before the initiation of the synthesis of structural proteins, a CTL response against these proteins could destroy the infected cells before the release of infectious virions.
AIDS Res Hum Retroviruses 1995 Nov
PMID:Helper and cytotoxic T cell responses of HIV type 1-infected individuals to synthetic peptides of HIV type 1 Rev. 857 90

Tat protein of HIV-1 is a potent transactivator of transcription and essential for HIV-1 replication. In addition, Tat has been proposed to possess immunosuppressive functions, suggesting that Tat may play a direct role in the immune dysfunction associated with AIDS. Recently, it has been reported that Tat represses activity of a major histocompatibility complex (MHC) class I gene promoter. Because HIV infection downmodulates expression of class I molecules, this data strongly suggests that Tat downregulates class I expression and leads to loss of CTL activity. Here, we report effects of Tat on class I expression using a human cell line, T0, expressing Tat (TO-Tat). Northern blot analysis shows that levels of MHC class I transcripts are normal in T0-Tat. Flow cytometry analyses indicate that expression of HLA class I molecules is not substantially downregulated to any great extent by Tat in T0-Tat. Further, pulse-chase experiments followed by Endoglycosidase-H treatment show that the rate of maturation and processing of class I molecules in T0-Tat is indistinguishable from that in the original cell line, T0. Taken together, these data suggest that Tat expression does not necessarily result in downregulation of class I expression.
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PMID:Effects of HIV-1 Tat on expression of HLA class I molecules. 860 59

Superantigens are a class of immunostimulatory molecules produced by bacteria and viruses. Their potent immune effects are due to their unique ability to bind to the major histocompatibility complex (MHC) outside the antigen-binding cleft and to stimulate T cells in a T-cell receptor (TCR) Vbeta-specific manner. Structural studies have revealed the binding sites involved in the MHC/superantigen/TCR complex. The bacterial superantigens are responsible for a number of syndromes, including food poisoning and toxic shock syndrome, but their effects may be not only acute but also chronic and complex. Recent evidence suggests that superantigens may be relevant to the pathogenesis of autoimmune and immunodeficiency disorders. To illustrate the detrimental effects of superantigens on disease outcome, evidence demonstrating the modulation of experimental allergic encephalomyelitis, an animal model for multiple sclerosis, by superantigen, as well as the potential role of superantigens in HIV pathogenesis of AIDS, will be presented. The information presented may provide valuable insight into the role of superantigens in autoimmunity and HIV infection.
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PMID:Superantigens: structure and relevance to human disease. 865 Feb 57

Adenovirus type 35 (Ad35) is an important pathogen in immunosuppressed individuals such as AIDS patients and bone marrow transplant recipients. Ad35, a member of Ad subgroup B, differs with respect to pathogenic properties from the more fully characterized subgroup C Ad, such as Ad2 and Ad5. One region of human Ad which varies between subgroups and which may influence Ad pathogenesis is early region 3 (E3), a region which appears to modulate the immune response to Ad infection. In order to begin to characterize the differences between the Ad35 E3 and the E3 of other Ad, the complete DNA sequence of the Ad35 E3 promoter and coding sequence along with two flanking structural proteins, pVIII and fiber, has been determined. Ad35 contains open reading frames which are unique to the subgroup B Ad in addition to the four characterized immunoregulatory proteins encoded by the subgroup C Ad. Further evaluation of the sequence of one of these proteins, 18.5K, which is the class-I major histocompatibility complex (MHC) binding protein of 18.5 kDa, demonstrates that the amino acid sequence of this Ad2 gp19K homologue fits a proposed model of gp19K-MHC interaction. Analysis of promoter sequences demonstrates that an NF-kappa B site found in the subgroup C E3 promoter is absent from the Ad35 E3 promoter. In addition, the fiber genes of Ad35 and other subgroup B Ad have been shown to diverge in an unexpected way, yielding three clusters of fiber homology.
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PMID:Sequence of the immunoregulatory early region 3 and flanking sequences of adenovirus type 35. 866 54

Toxoplasma gondii is a highly infectious intracellular parasite which, if left unchecked by the immune system, rapidly overwhelms its intermediate hosts, as illustrated by the pathogenesis of toxoplasmic encephalitis in patients with AIDS. In order to insure both its host's and consequently its own survival simultaneously, T. gondii induces a potent gamma-interferon (IFN-gamma)-dependent cell-mediated immunity early in infection that controls the replication of the protozoan and facilitates transformation into the dormant cyst stage. The protective IFN-gamma is derived from three sources: natural killer cells; and CD4+ and CD8+ T lymphocytes, which can partially compensate for each other in knockout mice lacking the appropriate major histocompatibility complex-restricting elements. At least two properties of the parasite appear to be responsible for the early induction of these effector cells. The first is a hydrophobic molecule (or group of related molecules) that triggers interleukin 12 (IL-12), tumour necrosis factor alpha and IL-1beta synthesis in macrophages. This response can also promote HIV replication in the same cells. The second is a superantigen activity that drives IFN-gamma-producing Vbeta5+ CD8+ T cells. These potentially lethal responses are later regulated through the triggering of IL-10 and by the induction of anergy in the superantigen-stimulated Vbeta5+ T cell population.
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PMID:Induction and regulation of host cell-mediated immunity by Toxoplasma gondii. 872 32

Among the various mechanisms proposed to explain the pathogenesis of cerebral lesions in human immunodeficiency virus (HIV)-induced encephalitis, a cytokine-mediated action has found most favour. Indeed, elevated expression of cytokines such as interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha), thought to be neurotoxic, has been found in AIDS patients. As a previous study had demonstrated the presence of HIV proviral DNA in brain tissue of a number of HIV-positive non-AIDS patients, we undertook this present investigation using morphological, immunohistochemistry (IHC) and polymerase chain reaction (PCR) methods to detect the expression of major histocompatibility complex (MHC) class II molecules, the presence of HIV-1 proviral DNA and of the cytokines TNF-alpha, IL-1 alpha, IL-4 and IL-6 in brains of the same group of individuals. The study included brains of 36 asymptomatic HIV-1 positive patients and the results were compared with those of AIDS patients either affected by HIV encephalitis (n = 8) or exempt from any neuropathological changes (n = 10) as well as of normal controls (n = 5). Results show that: HIV proviral DNA could be detected by PCR in 17 out of the 36 brains from HIV-positive pre-AIDS cases; most (15 of 17) of PCR-positive brains showed minimal to severe expression of MHC class II antigen; and cytokines could be detected predominantly within white matter even at this early stage. The data demonstrated that the state of immune activation described in AIDS is already present at the pre-AIDS stage and suggest that the presence of cytokines may already trigger the cascade of events leading to brain damage.
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PMID:Investigation on the expression of major histocompatibility complex class II and cytokines and detection of HIV-1 DNA within brains of asymptomatic and symptomatic HIV-1-positive patients. 874 Feb 30

We briefly review current evidence which indicates that major histocompatibility complex (MHC)-restricted, virus-specific cytotoxic T cells may be of immunological importance in protection from infection with immunodeficiency virus or with protection from disease progression which would finally result in acquired immunodeficiency syndrome (AIDS) and death. We suggest that prophylactic vaccines should elicit cytotoxic T lymphocyte (CTL) activity in naive individuals. Further, immunotherapy in infected individuals could be aimed at ensuring that levels of virus-specific CTL are kept high, broadening and redirecting their specificity towards conserved parts of the viral genome.
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PMID:Cytotoxic T cells--protection from disease progression--protection from infection. 881 56

We studied lumbosacral dorsal root ganglia (DRGs) from 10 patients with acquired immunodeficiency syndrome (AIDS) and five controls using immunocytochemistry, in situ hybridization and NADPH-diaphorase (NADPHd) histochemistry. Human immunodeficiency virus (HIV)-1 RNA was detected in five AIDS cases, and HIV-1 p24 antigen was found in four of these patients. The densities of nodules of Nageotte (nN), macrophages and major histocompatibility complex-class II-positive cells were significantly increased in the DRGs of AIDS patients compared to controls. Cytomegalovirus antigen was observed in the DRGs of four AIDS cases and one control, but without its presence being related to neuronal degeneration. Furthermore, we detected tumor necrosis factor, interferon-gamma, interleukin (IL)-1 beta, and IL-6 in the DRGs from AIDS patients. Using NADPHd histochemistry, we showed that the number of NADPHd-positive neurons was significantly increased in the DRGs of AIDS patients compared to controls, implying upregulation of nitric-oxide (NO) production in AIDS DRGs. Generally, there were increased numbers of nN in DRGs which contained more NADPHd-positive neurons. Additionally, immunoreactivity for an inducible form of NO synthase was detected in interstitial cells in AIDS DRGs. These results suggest that reactive inflammation, including the production of cytokines, occurs in the DRGs of AIDS patients and that excessive production of NO may be related to neuronal degeneration in AIDS DRGs.
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PMID:Increased NADPH-diaphorase reactivity and cytokine expression in dorsal root ganglia in acquired immunodeficiency syndrome. 881 58

There is increasing evidence that a disturbance of self-nonself-recognition plays an important role in the immunopathogenesis of AIDS. Here, Caner Susal, Volker Daniel and Gerhard Opelz speculate that the immune system is balanced between two groups of molecules that mimic major histocompatibility complex (MHC) proteins; AIDS is suggested to emerge as a consequence of human immunodeficiency virus (HIV) disturbing this balance in favor of anti-MHC class II responses.
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PMID:Does AIDS emerge from a disequilibrium between two complementary groups of molecules that mimic MHC? 882 Feb 68


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