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

Since alterations of epidermal Langerhans cells (LC) have been observed in humans infected with HIV, we investigated the morphology and function of these cells in murine acquired immunodeficiency syndrome (MAIDS), a murine model closely resembling human AIDS. The number as well as the shape of dendritic MHC class II+ cells from ear skin of C57BL/6 mice were similar in normal and infected animals. In mixed epidermal cell (EC) lymphocyte cultures, EC from infected mice and from normal mice stimulated allogeneic T cell proliferation to the same extent. In contrast to T cells from normal mice, however, T cells from infected mice did not respond to allogeneic spleen cells, confirming the presence of a T-cell defect in MAIDS. Subcutaneous injection of syngeneic mice with trinitrophenyl-modified MAIDS EC resulted in delayed ear swelling responses after challenge that were equivalent to those induced by hapten-modified EC from normal mice, suggesting that the contact sensitivity inducing potential of MAIDS LC was preserved. To investigate antigen presenting and processing function, EC and spleen cells were tested with the ovalbumin-specific IAb-restricted T cell hybridoma BO.17.10 and either ovalbumin 323-339 peptide or intact ovalbumin protein. MAIDS spleen cells had a reduced antigen presenting capacity compared with normal spleen cells, whereas EC from these mice showed the same processing and presenting capacity as normal controls. In summary, our results demonstrate that the frequency, morphology, level of MHC class II antigen expression and ability to process and present antigen is normal for LC from mice with MAIDS whereas the function of splenic T cells and APC from infected mice is significantly impaired.
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PMID:Epidermal and splenic antigen-presenting cell function in a retrovirally induced murine immunodeficiency syndrome (MAIDS). 132 74

Candidate AIDS vaccines consisting of recombinant forms of the HIV-1 envelope glycoprotein induce, in seronegative human volunteers, an env-specific T cell response that includes CD4+, MHC class II-restricted CTL capable of lysing HIV-1-infected target cells. In this study, we have analyzed the production of the cytokines TNF-alpha and lymphotoxin (LT) by a set of env-specific CD4+ human CTL clones. TNF-alpha and LT are of interest because of their potential role in target cell destruction by CD4+ CTL. Our studies focused on the possibility that a cell surface form of TNF-alpha expressed by CTL after physiologic activation with target APC might participate in the cytolytic reactions mediated by these clones. We found that, upon interaction with target cells expressing env epitopes in the context of the appropriate MHC class II molecules, CD4+ CTL released TNF-alpha with kinetics that were rapid, compared with other cytokines, and that were generally similar to the kinetics of target cell destruction. LT secretion was not detected during the time course of the cytolytic reactions. A novel flow cytometric assay was used to show that physiologic activation of CD4+ CTL with target APC induced expression by the CTL of cell surface forms of TNF-alpha. Immunoprecipitations from activated, surface-iodinated CTL clones revealed two forms of surface TNF-alpha, a 26-kDa form, representing the transmembrane precursor of secreted TNF-alpha, as well as the 17-kDa secreted form bound to the cell surface. For a subset of CD4+ CTL, we found that treatment of CTL with cyclosporin A inhibited Ag-induced production of both transmembrane and secreted forms of TNF-alpha but had no effect on cytolysis. Thus, although transmembrane and secreted TNF-alpha produced by HIV-1-specific CD4+ CTL may have important effects in vivo, the rapid destruction of target APC by the set of CD4+ CTL clones described here occurs through a TNF-alpha-independent mechanism.
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PMID:Production of transmembrane and secreted forms of tumor necrosis factor (TNF)-alpha by HIV-1-specific CD4+ cytolytic T lymphocyte clones. Evidence for a TNF-alpha-independent cytolytic mechanism. 135 Oct 88

The APC/stimulating cell (APC/SC) potential of PBMC from Walter Reed stage 1 and 2 patients and patients with AIDS was tested by using these PBMC as stimulators in an allogeneic MLR. The responding cells were PBMC from unrelated, HIV- donors that were either unfractionated or depleted of APC by plastic and nylon wool adherence. Using this approach, we observed no defect in the APC/SC potential of PBMC from Walter Reed stage 1 and 2 patients. However, PBMC from AIDS patients used as allogeneic stimulators exhibited three different patterns of APC/SC function: 1) no defect in alloantigen (ALLO) APC/SC potential; 2) a defect in ALLO APC/SC function that was detected only if the responder cells were depleted of APC (presenting cell defect); and 3) a defect in ALLO APC/SC function, irrespective of whether the responder cells were depleted of APC (stimulating cell defect). These results indicate that in addition to Th cell defects associated with AIDS, the PBMC from AIDS patients can also exhibit a defect in APC/SC function. This study provides an approach that permits the testing of Ag-presenting function in all AIDS patients, and is therefore not limited to testing patients for whom HIV-, HLA-identical T cells and APC are available.
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PMID:Multiple patterns of alloantigen presenting/stimulating cell dysfunction in patients with AIDS. 167 47

APC activity of spleen cells from C57BL/10 (B10) mice infected with LP-BM5 murine leukemia virus (MuLV), which is known as a murine acquired immunodeficiency syndrome (MAIDS) virus, was investigated. The ability of splenic APC from LP-BM5 MuLV-inoculated B10 mice to induce soluble Ag-specific proliferation of cloned Th cells was decreased progressively during the infection. The APC defect was found to be due neither to the decreased expression of Ia Ag nor to the insufficient production of IL-1. It was demonstrated that cloned Th stimulated with virus-infected splenic APC displayed the increased [Ca2+]i with severely decreased inositol phospholipid metabolism, which probably led to the defect of Th proliferative responses. These results suggested that the failure of Th to respond to soluble Ag in MAIDS is at least in part due to a selective defect in signal transduction caused by abnormal APC.
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PMID:A selective signaling defect in helper T cells induced by antigen-presenting cells from mice with murine acquired immunodeficiency syndrome. 215 66

Normal mice infected with 10(5) infectious doses of lymphocytic choriomeningitis virus (LCMV, WE isolate) generated a reduced or no T cell-independent IgM and/or T cell-dependent IgG response to a subsequent vesicular stomatitis virus Indiana (VSV-IND) injection; this transient immune suppression lasted for weeks to months. Connatally infected LCMV-carrier mice or acutely infected T cell-deficient nude mice had normal anti-VSV IgM and IgG or IgM responses respectively. LCMV-infected nude mice transfused with helper cell-depleted LCMV-specific immune spleen cells were immunosuppressed. Normal mice infected with LCMV but treated with a rat anti-CD8 mAb (that had been shown previously to eliminate cytotoxic T cells in vivo) and then infected with VSV exhibited a normal anti-VSV IgM and IgG response. Since no IFN-alpha or -beta was detected on, or after, day 6 of LCMV infection, neither LCMV alone, nor IFN induced by it caused the observed immune suppression; the presented evidence suggests that LCMV-immune CD8+ T cells were responsible for it. It is conceivable that a similar pathogenesis where virus-specific cytotoxic T cells may destroy virus-infected cells essentially involved in an immune response (APC, T helper cells, etc.) may be involved in other virally triggered immune suppression or in AIDS.
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PMID:Virus-triggered immune suppression in mice caused by virus-specific cytotoxic T cells. 296 46

In this paper we have attempted to define the role of suppressor T cells in many well-defined murine tumor systems. We have knowingly omitted a blocking antibodies, suppressor B cells as mediators of tumor immunosuppression in various murine tumor systems; these have been well reviewed elsewhere. Also, we have focused on the importance of two different types of antigen-presenting cells in the induction and suppression of cell-mediated immunity and on some of the different modalities employed to inhibit Ts function. Finally, we have discussed the acquired immunodeficiency syndrome and the possible role of a defective helper pathway and enhanced suppressor pathway in its pathogenesis. We and others believe that the suppressor pathway is preferentially activated by tumor antigen(s) in the cases of many immunogenic murine tumors--possibly due to the release of tumor antigen(s) from tumor cells, their subsequent trafficking to specific areas of the spleen and other organs, and, ultimately, their presentation by certain APC to Ts. Ts may then act directly upon helper Lyt 1+2- T cells as these cells interact with tumor antigen(s) on I-A+ APC. Alternatively, if the effector pathway were somehow impaired--e.g., by ultraviolet radiation or a virus--then the suppressor pathway may be activated in an unregulated manner, often to the detriment of the host. Biochemical characterization of the tumor antigens that stimulate Ts generation and, presumably, tumor growth and definitive documentation of a role of APC in the processing and presentation of these tumor antigens to Ts need to be done. Then selective stimulation of the effector immune response, along with inhibition of the suppressor response, to tumor antigens with drugs, monoclonal antibodies, and soluble mediators or their analogues may be possible in the near future.
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PMID:Suppressor T cells and the immune response to tumors. 623 15

APC dysfunction may be important in immune dysregulation associated with HIV disease. Langerhans cells, epidermal APC, can be infected with HIV, although their function in HIV-infected persons has not been studied. Therefore, we studied the immunologic function of Langerhans cells, in parallel with blood APC (enriched for monocytes/macrophages (M phi) function, in 21 HIV-seropositive (HIV+) and 21 HIV-seronegative volunteers, including three monozygotic twin pairs discordant for HIV serology. Langerhans cells from HIV+ patients were quantitatively normal and expressed normal levels of HLA-DR. However, Langerhans cells from AIDS patients and M phi from both AIDS and HIV+ non-AIDS patients stimulated allogeneic T cells less well compared with control APC. In addition, decreased recall Ag- and mitogen-induced T cell responsiveness was observed in HIV+ patients using either autologous Langerhans cells or autologous M phi as APC/accessory cells. Interestingly, Langerhans cells and M phi isolated from HIV+ twins (CD4+ cell counts of 181, 271, and 562/mm3) were able to present recall Ag normally to HIV-uninfected syngeneic T cells. In summary, APC from HIV+ patients were impaired in their ability to generate a primary immune response (i.e., alloantigen-induced T cell stimulation), but they retained the ability to generate a secondary immune response (i.e., recall Ag-induced syngeneic T cell stimulation). Thus, these findings suggest that defects in secondary immune responses commonly observed in HIV disease are dependent on T cell dysfunction alone, whereas defective primary immune responses may be secondary to both T cell and APC dysfunction.
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PMID:Functional studies of epidermal Langerhans cells and blood monocytes in HIV-infected persons. 789 31

An unusual case of a 67-year-old man is reported with fulminant pneumococcal sepsis. He had been healthy before, and the identified predisposing factors were only that he was a chronic alcohol drinker and was a HCV carrier. He presented signs of acute renal failure, liver dysfunction, adult respiratory distress syndrome and disseminated intravascular coagulation. Subsequently purpura fulminans (symmetrical peripheral gangrene) with major extremity involvement developed. He finally survived with amputation of both legs, right forearm and two fingers of left hand. Purpura fulminans is a rare catastrophic disease, with initial hemorrhagic skin lesions that progress to gangrene. It usually follows an infectious illness, and although it most commonly occurs in children, it can occur in adults with predisposing factors such as alcoholic, asplenia, AIDS and so on. In adults, pneumococcus and meningococcus are microorganisms that have been reported most frequently as caused agents in Europe and America. But in Japan the previously reported adult case was the only one complicating Xanthomonas maltophilia sepsis, and none accompanying pneumococcal sepsis. Congenital protein C deficiency is recognized to be able to cause purpura fulminans especially in patients with risk factors. In our case, protein C antigen was decreased in the acute stage but gradually increased later toward normal, so this decrease was thought to be concomitant with the initial disseminated intravascular coagulation rather than compatible with protein C deficiency.
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PMID:[Purpura fulminans complicating pneumococcal sepsis: a case report]. 796 3

The AIDS-associated lymphomas represent a heterogeneous set of disease processes. The largest histologic subset of lymphomas is the large-cell lymphomas, which represent a spectrum of disease processes ranging from monomorphic monoclonal B-cell proliferations to very polymorphic and polyclonal mixtures of B cells, T cells and macrophages. The next most frequent class of systemic lymphoma are the small non-cleaved cell or Burkitt's-like lymphomas. These are relatively monomorphic, monoclonal malignant B-cell proliferations. The final subset of lymphomas, which are likely to become more common as the AIDS epidemic progresses, are the primary CNS lymphomas, which are expansions of EBV-immortalized B cells. The high incidence of tumor-associated EBV in the CNS lymphomas makes these lesions somewhat analogous to an opportunistic EBV infection. In HIV disease there is a long lag after infection before the appearance of clinical manifestations of impaired T-cell immunity. During this period, both appropriate B-cell proliferation in response to antigen (including the ubiquitous HIV) and abnormal B-cell proliferation (autoimmune, dysregulated) occur as the follicular architecture is disrupted by the virus and potential APC are exposed and/or infected with HIV. The destruction of FDC or the involution of their processes could interfere with the elimination by apoptosis of low-avidity B-cell clones. Antigen-competent B cells with pre-existing chromosomal translocations such as the t(8;14) (c-myc, IgH) would have a selective growth advantage in this setting. Figure 9 shows a schematic representation of prelymphomatous and lymphomagenic events as they are projected to occur. A similar pathogenetic scheme has been postulated for follicular B-cell lymphomas: PCR studies have demonstrated that a pool of t(14;18) (IgH;bcl-2) B-cells are present in lymph nodes featuring follicular hyperplasia. In response to antigen (the evidence favoring antigen drive is extensive hypersomatic mutation in sequences related to binding sites), B cells with the t(14;18) translocation have a selective advantage because the bcl-2 oncogene confers a resistance to apoptosis. Burkitt's lymphomas, particularly sporadic or HIV variants, fulfill at least the key criteria for antigen competence, mainly the presence of surface Ig. The c-myc-associated chromosomal translocational events are likely to occur early during the enzymatic machinations of gene rearrangement. Such B cells would be in the dysregulated cytokine and antigen milieu of HIV disease and ultimately could have a selective advantage. EBV infection of B cells probably requires activation and expression of the CD21 receptor. Furthermore, CD5+ B cells of CLL are refractory to EBV infection.(ABSTRACT TRUNCATED AT 400 WORDS)
AIDS 1994 Aug
PMID:Pathogenesis of AIDS lymphomas. 798 99

T cell receptor (TCR) triggering via superantigens induces decreased proliferative responses and increased apoptosis in T cells from HIV-infected patients compared with controls. Our aim was to delineate the role of intrinsic T cell defects, of APC dysfunction and of cytokines and costimulatory signal dysregulation in the deficient responses of CD4+ and CD8+ T cells from HIV+ subjects to the superantigen Staphylococcus enterotoxin A (SEA). Proliferation and IL-2R alpha up-regulation on SEA-stimulated CD4+ and CD8+ T cells in whole blood were reduced in HIV+ subjects with CD4 counts < 500, compared with controls. Neither addition of IL-2, IL-12 or phorbol myristate acetate (PMA) nor neutralization of endogenous IL-10, tumour necrosis factor-alpha (TNF-alpha), TNF-beta or transforming growth factor-beta (TGF-beta) could restore the decreased activation by SEA. Possible intrinsic T cell defects were studied by presenting SEA on HLA-DR-transfected Chinese hamster ovary (CHO) cells, co-expressing LFA3 and/or CD80, to purified T cells. In this system CD8+ T cells from most HIV+ patients were hyporesponsive with regard to IL-2 production, IL-2R alpha up-regulation and proliferation, whereas clearly reduced responses were only shown in CD4+ T cells from AIDS patients. Similarly, apoptosis was increased in CD8+ T cells from all patients, but only in CD4+ T cells from AIDS patients. During HIV infection, the responses to TCR triggering through SEA are deficient in both T cell subsets. The intrinsic defect appears earlier during disease progression in purified CD8+ T than in CD4+ T cells, it occurs in conjunction with both CD2 and CD28 costimulation, and it is correlated with increased levels of apoptosis.
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PMID:Superantigen activation of CD4+ and CD8+T cells from HIV-infected subjects: role of costimulatory molecules and antigen-presenting cells (APC) 947 54


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