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O Pugliese

Publications and source records attributed to O Pugliese.

32 records · Page 2Linked to original sources

A gp120 HIV peptide with high similarity to HLA class II beta chains enhances PPD-specific and autoreactive T cell activation.

The recent report that anti-gp120 antibodies can be induced by allogeneic stimuli in experimental animals in the absence of HIV, has focused attention on the structural similarities between gp120 and MHC. Here we report that some HIV+ individuals develop antibodies which similarly react with the gp120 HIV sequence (aa 254-263) and with the HLA-DR beta chains (aa 142-151). As these two peptides share a high level of similarity, we have investigated the role of this gp120 region on HLA class II mediated T cell recognition. The synthetic peptide corresponding to the gp120 HIV sequence aa 254-263 has been tested on T cell line (TCL) activation. Both the PPD-specific and the self-HLA reactive TCL proliferation increased in the presence of this peptide. Prepulsing experiments indicate that this enhancing effect carried out by HIV peptide is exerted at the level of antigen presentation. Moreover, the specificity of this interaction is supported by the fact that a MoAb specific for this HIV peptide blocked the autoreactive TCL proliferation, similarly to the inhibition carried out by anticlass II antibody. These data support the hypothesis that the functional homology between the HIV peptide and the HLA beta chain described may be involved in the pathogenesis of AIDS.

Amino Acid Sequence↗

Natural killer cell frequency and function in patients with monoclonal gammopathies.

We evaluated the frequency and the functional activity of peripheral blood mononuclear cells (PBMCs) with natural killer (NK) cell phenotype in patients with monoclonal gammopathies. CD16+ and CD56+ PBMCs were strongly increased in monoclonal gammopathies of undetermined significance (MGUS) and multiple myeloma (MM). Furthermore, increased frequency of CD16+/CD3+ PBMCs was found in 7/15 patients with MGUS, indicating that T lymphocytes with NK-like phenotype are expanded in at least a subset of these patients. However, despite the increased frequency of PBMCs with natural killer phenotype, the functional NK activity was as comparable in both MGUS and MM patients as in normal individuals. The discrepancy between the expansion of circulating NK cells and the normal NK activity in patients with monoclonal gammopathies requires further investigation. However, at least in some MGUS patients, this discrepancy could be accounted for by the expansion of PBMCs with the rare phenotype CD16/CD3 which have been reported not to mediate significant NK activity.

Aged↗

[The expansion of NK CD56+ cells with reduced cytotoxicity in a female patient with systemic sclerosis].

An absolute and relative increase of circulating CD56+ (NKH1, Leu19) natural killer cells has been found in a patient with systemic sclerosis. The expanded natural killer cells exhibited reduced natural killer activity and antibody-dependent cell-mediated cytotoxicity. Furthermore, the limiting dilution analysis of spontaneous in vitro immunoglobulin synthesis demonstrated that the precursor frequency of immunoglobulin-secreting cells and the "single-hit" kinetics of the titration curve were similar to healthy controls, but strongly different from previously reported patients in whom CD16+NK cell subset was expanded. Thus, our findings might suggest that expanded CD56+ natural killer cells exhibit unique regulatory properties on B cell function in systemic sclerosis.

Aged↗

A limiting-dilution analysis of activated circulating B cells in Crohn's disease.

In the present study the spontaneous in vitro production of immunoglobulins G, A, and M by peripheral mononuclear cells was evaluated, in patients with Crohn's disease, in relation to the state of B-cell activation and further characterized by limiting-dilution analysis. A total of 25 patients with Crohn's disease and 10 healthy controls was studied. The proportion of the transferrin receptor-bearing cells in the B7+ subset was higher in active Crohn's disease patients than in either those with quiescent disease or controls. There was a significant rise in the in vitro IgG, IgM, and IgA production in patients with untreated active Crohn's disease compared to either those with untreated quiescent disease or controls. When patients were followed up from the active phase to clinical remission, a significant decrease in the production of IgG and IgM was observed. IgA levels also showed a decrease, although not reaching statistical significance. When the Ig production was analyzed by limiting dilution, no difference was observed between patients and controls in terms of either precursor frequency of Ig-producing cells or patterns of frequency distribution. In both patients and controls a biphasic limiting-dilution profile was observed. This study shows that a significant B-cell activation is present in Crohn's disease patients, which is accompanied by an increase in immunoglobulin production. This study also indicates that in Crohn's disease the increased immunoglobulin production is related to an augmented B-cell clone size rather than to an increased precursor frequency.

B-Lymphocytes↗

Regulation of self-major histocompatibility complex reactive human T-cell clones.

The proliferative response of human T-lymphocyte clones, (TLC) specific for self-major histocompatibility complex (MHC) products either alone or associated with PPD epitopes are inhibited in vitro by dexamethasone (DEX) and by a non-specific inhibitory factor(s) (nsINH) produced by PPD-activated T-cells. The inhibiting effect has been investigated by preincubating autoreactive and PPD-specific TLC with nsINH or DEX. Results obtained indicate that T-lymphocytes are the target of these two immunoregulatory molecules. Moreover, the addition of exogenous recombinant interleukin 2 (rIL-2) substantially reverses the inhibition observed in both nsINH- or DEX-treated cultures.

Antigens, Bacterial↗

Increased autoreactive T cell frequency in tuberculous patients.

The development of putative self-MHC-reactive T cells and their precursor frequency was estimated in peripheral blood lymphocyte cultures stimulated in vitro with PPD. The role of foreign antigen in the generation of self-MHC-reactive T cells in vivo was analyzed by comparing the frequency of autoreactive T cells in the peripheral blood of tuberculous patients with that observed in healthy individuals. It was found that PPD in vitro and Mycobacterium tuberculosis infection in vivo increased substantially the generation of autoreactive T cells. Autoreactive T cell clones were shown (1) to recognize self MHC class II products; (2) to release gamma interferon in the absence of exogenous antigen, and (3) to express autocytotoxic activity. All these findings suggest that self-MHC-reactive T cells may be involved in the inflammatory response to M. tuberculosis.

Cells, Cultured↗

Immunoregulatory effect of a synthetic peptide corresponding to a region of protein p24 of HIV.

The effect of a synthetic peptide, corresponding to a sequence of HIV-1 p24 protein (amino acids 218-237), on in vitro immune responses was studied. The peptide inhibited in a dose-dependent manner the induction of an anti-SRC antibody response and of a PPD-specific proliferative response of human PBL. On the other hand, PHA-induced proliferation of human PBL and PPD-induced proliferation of a PPD-specific human T-cell line were not modified by comparable amounts of the peptide. These results suggest that structures from a protein (p24), present in the serum throughout the course of HIV infection, are able to interfere with the inductive stages of specific immune responses. These findings may help to unravel some of the pathogenic mechanisms of AIDS and may contribute to the development of vaccine strategies.

Animals↗

Familial predisposition to discogenic low-back pain. An epidemiologic and immunogenetic study.

The first-degree relatives (parents, siblings and children) of 284 patients complaining of discogenic low-back pain (Group I), 114 patients who had undergone surgery for lumbar disc herniation (Group II), and 280 individuals who had never complained of low-back pain (Group III) were surveyed by self-completed questionnaires. Of the families in Group I and Group II, 35 and 37%, respectively, had at least one member with a history of discogenic back pain and 5 and 10%, respectively, had one or two members who had undergone disc surgery. Of the asymptomatic subjects in Group III, only 12% had at least one or more affected relatives and 1% had a relative who had undergone disc surgery; of the affected families, 41% had two or more members with a history of back pain. The proportion of symptomatic relatives in the affected families was higher among sedentary workers and motor vehicle drivers than among heavy or light manual workers. An immunogenetic study comparing the frequencies of HLA-A, B, and C antigens in 39 patients who had undergone lumbar disc surgery with those in 60 asymptomatic individuals showed no significant differences between the two groups. This study indicates that there is a strong familial predisposition to discogenic low-back pain, and suggests that the etiology of degenerative disc disease is related to both genetic factors, not linked to the HLA antigen system, and environmental factors.

Adult↗

Mechanism of action of an antigen nonspecific inhibitory factor produced by human T cells stimulated by MPPS and PPD.

Human T lymphocytes cultured in vitro for 5 days with C. albicans purified polysaccharide (MPPS) and with purified protein derivative (PPD) from M. tuberculosis produce an antigen nonspecific inhibitory factor(s) (nsINH). nsINH blocks antigen-driven cell proliferation and the development of natural killer cells (NK) when added at the beginning of peripheral blood mononuclear cell culture. Analysis of the mechanism of action shows that nsINH inhibits the production of interleukin 2 (IL-2), the expression of IL-2 receptor (Tac antigen), and the synthesis of immune interferon (IFN). The biochemical characterization of nsINH shows that the suppressive activity is acid (pH 2.5) and temperature (56 degrees C) resistant. Gel filtration analysis indicates a molecular weight of 30-35K and 60-65K. These results suggest a role for nsINH in the down regulation of the lymphokine cascade.

Candida albicans↗

A purified polysaccharide isolated from Candida albicans induces antibody response in vitro by human peripheral blood lymphocytes and discriminates between sera from normal and Candida albicans-infected individuals.

A purified polysaccharide extracted from Candida albicans (MPPS), stimulates in vitro synthesis of specific antibodies by human peripheral blood lymphocytes. These antibodies can be detected by a sensitive enzyme-linked immunoassay. The same assay can be applied to the quantitation of anti-candida antibodies in serum. Statistically significant differences were found between sera of normal and candida-infected individuals.

Adult↗

Preparation of liposomes incorporating membrane components from human lymphoid cells.

A procedure for the preparation of liposomes incorporating membrane components of human lymphoid cells is described, whereby the detergent used to solubilize the plasma membrane is almost completely eliminated. MHC products HLA-A-B-C and DR molecules were shown to be incorporated into the liposomes and their antigenic determinants to be exposed on the outer surface. A protein-rich liposomal fraction could be separated from both protein-free liposomes and from aggregates. This preparation may be suitable for testing the functions of cell membrane components in biological assay systems.

Antigens, Neoplasm↗

Production of xenoantiserum to a chemically induced murine tumor: analysis of tumor specificity in different immune tests.

The method of in vivo absorption of xenoantisera raised against murine chemically-induced tumors has been used to obtain specific anti-tumor sera. To assess if the tumor specificity was maintained under different experimental conditions, the sera were employed in in vitro tests based on different immunologic reactions. In vivo absorption results in the production of xenoantisera which are highly specific for the immunizing tumor and that lack antibody activity toward histocompatibility and organ specific antigens and endogenous virus antigens. Thus, in vivo absorbed antisera appear to be valuable reagents for the immunochemical characterization of chemically-induced tumors.

Absorption↗

Apoptosis in HIV infection: protective role of IL-2.

Peripheral blood mononuclear cells from HIV-infected subjects have been demonstrated by different methods to die by apoptosis after short time in culture. In the present study the percentages of apoptotic cells have been measured by propidium iodide staining and flow cytometry in PBMC from healthy controls (15) and HIV-infected subjects with asymptomatic (10) or advanced (15) disease, with or without anti-viral treatment. The percentage of apoptosis significantly correlated with clinical stage (CDCII: 15.85% +/- 9.17, CDCIV: 22.6% +/- 5.97, P < 0.001) and the CD4/CD8 CD3 cell ratio. R = -0.57, P = 0.012), while no differences were found in relation to AZT therapy. By adding IL-2 to the cultures the percentages of apoptosis of PBMC from HIV-infected patients were significantly reduced in all experiments.

Apoptosis↗