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

Recognition of viral Ag and of the envelope glycoprotein of HIV (gp120) in particular by human Th cells is critical in the immune response to the viral Ag which includes antibody production and generation of cytotoxic cells. Procedures to increase antigenicity of gp120 are highly desirable in a vaccine perspective. Therefore, to induce activation of gp120-specific T cells by a liminal dose of Ag we enhanced uptake of gp120 by exploiting the galactose receptors on APC. Terminal sialic acid residues were removed by neuraminidase treatment from the carbohydrate side chains of the heavily glycosylated gp120. Galactose residues were exposed and hence recognized by galactose receptors on APC. The experiments demonstrated that 1) human monocytes and dendritic cells, but not cells of the B lineage, bear galactose receptor; 2) galactose receptors are indeed involved because enhanced presentation is inhibited by galactose and acetylgalactosamine and competed for by other asialoglycoproteins; 3) galactose receptors mediate internalization of Ag in intracellular compartments that intersect the processing and presenting pathways, resulting in activation of specific T cells; 4) antigenicity of gp120 for specific T cells can be enhanced by the exposure of galactose residues.
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PMID:Galactose receptors and presentation of HIV envelope glycoprotein to specific human T cells. 131 6

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

We have developed a modified solvent/detergent (S/D) treatment to inactivate viruses in human plasma using 1% w/w final concentration of tri(n-butyl) phosphate (TNBP) and Triton X-100 and an incubation period of 4 h at 30 degrees C. The procedure inactivates > or = 10(6) chimpanzee-infectious doses (CID50) of HBV, > or = 10(5) CID50 of HCV, and > or = 10(6.2) tissue culture infectious doses (TCID50) of HIV. After virus inactivation, eleven plasma batches were lyophilized and 12 batches were deep-frozen until further use. The batches were characterized by extensive laboratory tests including measurement of clotting factors I-XIII, von Willebrand factor, plasminogen, inhibitors of blood coagulation and fibrinolysis, and other clinically important plasma proteins. All parameters were determined before and after S/D treatment. Twelve conventional single donor plasma units served as control. There were no marked losses of activities of clotting factors, antithrombin III, protein C, plasminogen, and C1-esterase inhibitor due to treatment. After the S/D step, the levels of these parameters were within the normal range in all batches. The same holds true for total protein, immunoglobulins, albumin, complement factors C3 and C4, haptoglobin, hemopexin, caeruloplasmin, alpha 1-antitrypsin, and pH. Protein S and alpha 2-antiplasmin activities decreased by about 50% and were frequently found to be slightly below the lower limit of the respective normal range after treatment. The interindividual variations of all proteins analysed were significantly lower than in the single donor plasma units. The S/D procedure did not lead to increases of markers indicating activation of hemostasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Manufacture and in vitro characterization of a solvent/detergent-treated human plasma. 144 62

Human T cell lines specific for different peptides of HIV envelope glycoprotein gp120 have been used as probes to identify the availability of functional MHC-peptide complexes on APC. MHC-peptide complexes recognized by T cells specific for peptide 24 (amino acids 225-240) are no longer available on the surface of APC after interaction with irradiated (binding nonproliferating) T cells with the same fine specificity. On the contrary, MHC-peptide complexes recognized by T cells specific for peptide 30 (amino acids 285-300) were functionally available and could stimulate T cells with such a specificity. The reciprocal experiment yielded similar results. The same data were also reproduced with another pair of gp120 peptides. These data demonstrate that upon clustering of peptide-specific T cells with presenting cells presentation of the same peptide to a second cohort of T cells with identical specificity is abolished, suggesting that a selective functional depletion of the MHC-peptide complexes engaged with specific T cells occurs at the surface of the presenting cells. The depletion does not affect other MHC molecules complexed with unrelated peptides.
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PMID:Selective functional depletion of HIV gp120 peptides complexed with MHC from antigen-presenting cells engaged with specific T lymphocytes. 163 69

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

Monocyte/macrophages (MM) were isolated from HIV-1 seronegative individuals, infected with HIV-1 and examined for their ability to infect autologous T lymphocytes with and without concomitant presentation of exogenous Ag. HIV-1-infected MM presented tetanus toxin (TT) and streptokinase to T cells (as measured by [3H]thymidine incorporation) comparable to presentation by uninfected MM. In these studies, it was observed that HIV-1-infected MM without additional exogenous Ag stimulated autologous T lymphocytes, however, to a lesser degree than with TT and streptokinase. Virus production in T cells appeared to be relative to the degree of stimulation with the highest levels of stimulation and infection observed when T cells were exposed to HIV-1-infected TT-presenting MM. Studies were carried out to examine some of the restricting elements in MM-mediated infection of T lymphocytes with and without TT presentation. Antibodies to CD4, as well as soluble immunopurified gp120, blocked cell-mediated infection indicating that infection of T cells was through the CD4 molecule as has been demonstrated with cell-free virus. In addition, soluble gp120 inhibited Ag presentation by HIV-1-infected and uninfected MM. mAb to MHC class II Ag HLA-DR and -DP blocked T cell infection by HIV-1-infected MM with and without presentation of TT. No effect was observed with mAb to MHC class I Ag. These results indicate that virus transmission to T lymphocytes can be mediated by HIV-1-infected MM and that these cells maintain their function as APC. Activation of T cells appears to be important in the process of T cell infection in this system inasmuch as antibodies that block Ag presentation and thus a T cell proliferative signal inhibit infection.
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PMID:HIV-1 transmission and function of virus-infected monocytes/macrophages. 169 Feb 36

The envelope glycoprotein of HIV gp120 is a T cell Ag in experimental animals and in humans infected with HIV or deliberately immunized with gp120 in various forms. Inasmuch as T cell responses result from the interaction of Ag processed and presented by APC with the unprimed T cell repertoire, we have investigated the human T cell repertoire specific for gp120 in seronegative, normal individuals. T cell lines and clones specific for HIV gp120 were generated by repeated in vitro stimulation of peripheral blood T lymphocytes with gp120-pulsed APC, followed by IL-2 expansion. We observed that the T cell response to whole gp120 involved single restricted immunodominant epitopes in gp120 that differ between responding individuals. Focusing of the response to limited regions of gp120 when the whole Ag is used for priming suggests that one or more adjacent epitopes are immunodominant and mask responses to "immunorecessive" epitopes. We have been able to generate primary in vitro responses to recessive epitopes by stimulation in vitro with synthetic peptides of gp120. The results indicate that a much broader T repertoire can be detected when individual peptides are used for priming in vitro rather than gp120. This information has important implications for the development of vaccination protocols aimed at eliciting diverse immune responses to "immunorecessive" regions of envelope glycoprotein.
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PMID:The naive repertoire of human T helper cells specific for gp120, the envelope glycoprotein of HIV. 170 85

A possible component of the immune dysfunction associated with infection by HIV is the inhibition of CD4 function resulting from the avid binding of soluble HIV envelope glycoprotein (gp120) to cell surface CD4. We assessed CD4 function by measuring the ability of CD4+ T cells to form conjugates with cell size lipid vesicles, artificial target cells (ATC), bearing the natural ligand for CD4, MHC class II proteins. Conjugate formation was a transient process with the greatest number of specific cell to ATC conjugates found after approximately 30 min of incubation at 37 degrees C. Addition of gp120 specifically blocked conjugates between CD4+ cells and class II ATC in a concentration-dependent manner. These data indicate that T lymphocyte adhesion mediated by CD4 is a dynamic event and that binding of gp120 to CD4 is able to disrupt the normal progression of the interaction between CD4+ T lymphocytes and class II+ APC.
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PMID:HIV-gp120 can block CD4-class II MHC-mediated adhesion. 196 69

The propensity of HIV-1 to undergo sequence variation, particularly in the envelope glycoprotein gp120, complicates vaccine development and may enable the virus to evade ongoing immune responses in infected individuals. We present here a molecular analysis of the effects of this variability on human T cell recognition of HIV-1 gp120. Synthetic peptides representing a defined CD4+ human T cell epitope in gp120 were used to survey gp120 molecules from various HIV-1 strains for the capacity to be recognized in the context of a single human MHC molecule, DR4. Variation affected recognition at two levels. For some strains, variation in this epitope was sufficient to alter the interaction of Ag receptors on gp120-specific human T cell clones with peptide-DR4 complexes on APC. In the case of two strains, the natural variation was sufficient to prevent the critical initial interaction between the relevant gp120 peptides and DR4 on the APC. However, these strains were highly divergent from the reference strain. Thus it is encouraging to note that the range of natural sequence variation in this T cell epitope falls, for the most part, within the range of peptide sequences that can be accommodated by the relevant human MHC molecule.
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PMID:Genetic variability in HIV-1 gp120 affects interactions with HLA molecules and T cell receptor. 197 Mar 52


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