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Biomedical subjects

L Nencioni

Publications and source records attributed to L Nencioni.

At least 55 records · Page 3Linked to original sources
PubMed1988

Comparative analysis of immunological responses to oral (Ty21a) and parenteral (TAB) typhoid vaccines.

The clinical and immunological responses to typhoid vaccination with parenteral (TAB) and oral (Ty21a) vaccines in two groups of 30 adult male subjects were studied. Parameters monitored included specific anti-Salmonella typhi cell-mediated immunity and total and specific antilipopolysaccharide fecal immunoglobulin A (IgA) titers in Ty21a-vaccinated subjects. Peripheral blood lymphocytes antibacterial activity was significantly increased only in Ty21a-vaccinated subjects. Serum arming activity and results of human F(ab')2 anti-IgG and -IgA inhibition tests suggest antibody-dependent cellular cytotoxicity mediated by IgA in those vaccinated with Ty21a. Interestingly enough, the cells of TAB-vaccinated subjects were able to mediate IgG-dependent cellular cytotoxicity, as was observable from the results of blocking experiments. Moreover, total and specific antilipopolysaccharide fecal IgA levels were observed to be significantly increased with Ty21a, up to 8 months post-vaccination schedule. An early-onset, transitory increase in serum IgM rheumatoid factor was also found, exclusively in subjects treated with TAB, and was no longer detectable on day 240. Ty21a was well tolerated and free of side effects, whereas 65% of subjects administered TAB reported fever, headache, malaise, and local tenderness at the injection site. Our data show that the two typhoid vaccines induce different cell-mediated specific immune responses. The role of these responses in protection against Salmonella infection, however, requires further investigation.

Administration, Oral↗
PubMed1988

IgA-driven antibacterial activity against Streptococcus pneumoniae by mouse lung lymphocytes.

To investigate the role of lung lymphocytes (LL) in the local defense mechanisms, we studied the natural antibacterial (NA) activity of mouse LL with an in vitro assay using S. pneumoniae type 3 as target. In parallel, natural killer (NK) activity against YAC-1 tumor cells was investigated. Lung cells obtained by enzymatic digestion were found to exert detectable NA and NK activities, which were further increased after purification of LL (greater than 90% lymphocytes) by carbonyl iron and magnet treatment. Depletion experiments with antibodies and complement indicated that the effector cell of NA activity was a Thy 1.2+, L3T4+, aGM1+ lymphocyte, whereas the effector of NK activity was found to have a Thy 1.2-, aGM1+ phenotype. Preincubation of LL with anti-IgA antibodies, but not with anti-IgG, completely inhibited NA activity, suggesting that it was mediated by preexisting IgA bound to the LL surface. Furthermore, purified IgA from S107 plasmacytoma with specificity for phosphorylcholine, a component of the outer wall of S. pneumoniae, was able to enhance the antibacterial activity of LL and to restore their activity after treatment with anti-IgA. In addition, S107 antibodies were found to specifically induce antibacterial activity against S. pneumoniae in resident alveolar macrophages (AM) and peritoneal exudate cells, which did not express NA activity. We conclude that mouse LL include a subset of IgA-bearing lymphocytes with the phenotype of helper-T cells, which are able to exert NA activity against pneumococcus through an IgA-driven mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Enhancement of in vivo immune response by tumor necrosis factor.

Interleukin 1 (IL-1) has been shown to regulate several immunologic functions. Since tumor necrosis factor (TNF) shares many biologic properties with IL-1, we have investigated here the role of TNF in the modulation of the immune response. We have thus tested low doses of human recombinant TNF-alpha (hu rTNF-alpha) for its capacity to enhance the in vivo antibody responses evaluated at the cellular level in the hemolytic plaque assay. It was found that hu rTNF-alpha, like human IL-1 beta, is able to enhance the immune response to a T cell-dependent antigen (sheep red blood cells). Interestingly, at variance with human recombinant IL-1 beta, hu rTNF-alpha was not able to enhance the in vivo antibody response to a T cell-independent antigen (type III pneumococcal polysaccharide). These results suggest that low levels of TNF may have a role in the modulation of the immune response in vivo and shed new light on the biologic significance of this mediator.

Animals↗
PubMed1987

In vivo immunostimulating activity of the 163-171 peptide of human IL-1 beta.

The stimulating effect of a synthetic nonapeptide (fragment 163-171) of human interleukin 1 beta (IL-1 beta) on antibody responses to both T helper-dependent and T helper-independent antigens was investigated. It was shown that the nonapeptide enhanced the antibody response, as evaluated in the hemolytic plaque assay, of spleen cells from mice immunized with sheep red blood cells (SRBC). The activity of the 163-171 peptide on the primary response to SRBC was dose-dependent, being maximal when the peptide was inoculated at 100 mg/kg together with the antigen. Moreover, the 163-171 peptide was also effective in enhancing the secondary response to SRBC. The effect of the 163-171 peptide was to augment the frequency of cells specific for the antigen, inasmuch as no increase was ever observed in spleen cell numbers after treatment. In all these studies, human recombinant IL-1 beta gave effects qualitatively comparable to those of the 163-171 peptide, with a maximal activity at 20 ng/kg. Both the 163-171 peptide and human recombinant IL-1 beta were also able to enhance the in vivo immune response to a T helper-independent antigen such as SIII, a poorly immunogenic polysaccharidic antigen from Streptococcus pneumoniae type III. It can therefore be proposed that this synthetic nonapeptide of human IL-1 beta may represent a good candidate for use as adjuvant in vaccines.

Adjuvants, Immunologic↗
PubMed1987

Adjuvant activity of the 163-171 peptide of human IL-1 beta administered through different routes.

The synthetic peptide VQGEESNDK, corresponding to the fragment 163-171 of human IL-1 beta, could potently enhance the primary and secondary response of mice immunized with SRBC, measured as the number of specific antibody-secreting cells in the spleen. This adjuvant activity was dose-dependent, being maximal when the nonapeptide was administered intraperitoneally (i.p.) or subcutaneously (s.c.) at 100 mg/kg or orally (p.os) at 33 mg/kg, reaching levels comparable to those attained by 20 ng/kg of hu rIL-1 beta given i.p. or s.c. A dose-dependent enhancement of the primary response to SRBC was also observed when IL-1 beta or its peptide fragment were injected intravenously (i.v.) together with the antigen, with a maximum activity at 10 micrograms/kg for the 163-171 peptide and 100 pg/kg for hu rIL-1 beta. Thus, the in vivo immunostimulatory activity of hu IL-1 beta depended on the administration route as follows: i.v. much greater than s.c. = i.p. much greater than p.os. Conversely, the adjuvant effect of the 163-171 peptide was: i.v. much greater than p.os greater than s.c. = i.p.

Adjuvants, Immunologic↗
PubMed1986

IgA-driven T cell-mediated anti-bacterial immunity in man after live oral Ty 21a vaccine.

Cellular immunity against Salmonella typhi was observed by using a direct anti-bacterial in vitro assay in volunteers orally vaccinated with the live S. typhi mutant strain Ty 21a. With this experimental approach, it was demonstrated that Ty 21a vaccine also induces cellular immunity against S. paratyphi A and B. Interestingly, the mechanism involved in cellular immunity against bacteria seems to be of an antibody-dependent cellular cytotoxicity (ADCC) type, with IgA acting as the humoral arm and CD4+ T lymphocytes as the cellular one. In accordance with the increase in IgA-driven ADCC against S. typhi, a major rise in IgA against O and H antigens was observed in the serum of vaccinees in parallel to an increase in IgG of identical specificity. Furthermore, a Ty 21 vaccine induced cellular activity against flagellar antigens. These results indicate that IgA-ADCC by T lymphocytes against bacteria can originate from local stimulation of the gut mucosal immune system. This cellular defense mechanism might be at the origin of the protection induced by Ty 21a vaccine.

Administration, Oral↗
PubMed1985

Modulation of in vitro natural cell-mediated activity against enteropathogenic bacteria by simple sugars.

Lymphoid cells from mouse Peyer's patches and spleens were tested in a 2-h in vitro assay for their natural activity against the enteropathogenic bacteria Salmonella typhimurium, Salmonella enteritidis, Salmonella tel aviv, and Shigella sp. X16. The antibacterial activity expressed by normal cells was detected against all the bacterial strains tested with the exception of Peyer's patch lymphocytes against S. tel aviv and splenocytes against Shigella sp. X16. To determine whether the different expression of natural antibacterial activity might be due to lectin-like proteins interacting with the saccharidic moieties of the bacterial wall, 11 simple sugars were preincubated with the effector cells before the in vitro assays. We found that some of them could block the natural antibacterial activity as well as induce antibacterial activity when this was not spontaneously expressed. Interestingly, a different panel of sugars among those employed was observed to affect the antibacterial activities for each of the above-mentioned bacterial targets and each effector cell. However, the same panel of sugars was able to block or stimulate the lymphocyte activity when bacteria with the same somatic antigens as two substrains of S. typhimurium and one strain of Salmonella schottmuelleri were employed. To further investigate the interaction between effector cells and bacteria, effector cells or Shigella sp. X16 targets were treated with proteolytic, glycolytic, and lipolytic enzymes before the in vitro assays. Furthermore, EDTA was used to analyze the role of divalent cations in this experimental system. The results obtained suggest that lectin-like proteins playing a role in this interaction are present not only on lymphocytes but also on bacteria and that divalent cations are essential for the expression of in vitro antibacterial activity.

Animals↗
PubMed1985

Cellular immunity against Salmonella typhi after live oral vaccine.

Seventeen adult volunteers were vaccinated orally with the live attenuated Salmonella typhi mutant strain Ty21a. Their peripheral blood mononuclear cells were tested at different times after vaccination for direct cell-mediated activity against bacteria, employing a simple short-term in vitro assay. It was observed that 16/17 of the vaccinated subjects acquired the capacity to express specific cellular immunity against S. typhi which lasted from 15 days to at least 3 years. The effector cell of the in vitro antibacterial activity was preliminarily characterized as a non-adherent T3+, T8-, T4+ lymphocyte. In parallel, mice immunized orally with S. typhimurium and proving resistant to reinfection were tested employing the same in vitro assay. Also in this case peripheral and, most important, intestinal lymphocytes were able to express cellular immunity against the agent of murine typhoid. It is concluded that administration of live oral vaccine against S. typhi results in the induction of specific cellular immunity which is expressed at the peripheral and, probably, also at the intestinal level.

Adult↗
PubMed1985

Natural anti-bacterial activity against Salmonella typhi by human T4+ lymphocytes armed with IgA antibodies.

Peripheral blood mononuclear cells from normal volunteers possess natural anti-bacterial (NA) activity against S. typhi that can be measured in a 2-hr in vitro assay. Employing fractionation on nylon wool columns, Percoll gradients, plastic adherence, and E rosetting, the effector cell of NA activity appeared to be a lymphocyte of the T lineage rather than a macrophage, a B lymphocyte, or a large granular cell. Moreover, complement-dependent killing with monoclonal antibodies such as OKM1, OKB7, OKT8, 5.9 and the anti-natural killer cells AB8.28 did not reduce NA activity. On the contrary, this was completely inhibited when OKT3, OKT11, or OKT4 antibodies and complement were used to pretreat the effector lymphocytes. Indeed, T4+ cells sorted with a FACS displayed an extremely high NA activity against S. typhi. By pretreatment of peripheral lymphocytes with F(ab')2 fragments against human IgA, the NA activity was blocked. It is therefore suggested that NA activity by human cells might be a mechanism of defense against infections, acting as antibody-dependent cellular cytotoxicity expressed by T4+ lymphocytes coated with preexisting anti-Salmonella IgA antibodies.

Antibodies, Bacterial↗
PubMed1984

Identification and synthesis of an antigenic determinant common to human chorionic somatomammotropin and human growth hormone.

Human chorionic somatomammotropin (hCS) and human growth hormone (hGH), despite their different biological activities, show a remarkable degree of homology in their primary structure, which explains their immunological cross-reactivity. On the basis of the hydrophilicity profiles, we predicted that the sequence 165-174 would correspond to an antigenic determinant common to both hormones. The sequence 165-174 was synthesized in the solid phase and the ability to bind antibodies to hCS was tested by a radioimmunoassay at each step of the synthesis, without detaching the peptide from the resin. We found that the immunological sequence able to bind antibodies to hCS is that corresponding to 167-174. In similar experiments, we showed that the sequence 166-174 is able to bind antibodies to hGH. In the plaque-forming cell test using the synthetic fragment 166-174 bound to sheep red blood cells, we also observed that the ratio between the number of cells forming antibodies to hCS and to the 166-174 peptide was always between 0.45 and 0.73, thus suggesting that the 166-174 peptide represents a major determinant of hCS.

Amino Acid Sequence↗
PubMed1984

IgA-dependent cell-mediated activity against enteropathogenic bacteria: distribution, specificity, and characterization of the effector cells.

Antibody-dependent cellular cytotoxicity (ADCC) against murine enteropathogenic bacteria such as Salmonella typhimurium and Salmonella tel aviv or Shigella X16 was assessed by using IgG, IgA, and secretory IgA (sIgA) in a 2-hr in vitro assay where peripheral and intestinal lymphocytes were used as effector cells. It was found that IgG could arm splenocytes (SpL) better than IgA. However, IgG did not arm lymphocytes from Peyer's patches (PPL) or from mesenteric lymph nodes (MnL), whereas IgA of plasmacytoma origin against S. tel aviv and purified intestinal sIgA against Shigella X16 induced specific antibacterial ADCC with both SpL and PPL. When sIgA were tested with intestinal lymphocytes from the epithelium and the lamina propria, i.e., cells from the gut mucosa which first interact with enteric bacteria, it was found that both these lymphoid populations were able to express sIgA-dependent ADCC against Shigella X16. In parallel tests, cells from thymus and popliteal lymph nodes failed to express ADCC. Blocking studies with purified IgG and IgA of goat, rabbit, and mouse origin demonstrated that the Fc-alpha and Fc-gamma receptors were specifically involved in IgA- or IgG-dependent antibacterial ADCC. At least two effector populations, a macrophage and a Thy-1.2- lymphocyte, were observed to exert IgA-ADCC at the splenic level, whereas only lymphoid cells expressed this activity at the GALT level. Together, these results describe a new activity of IgA against enteropathogenic bacteria.

Animals↗
PubMed1984

Genetic control of in vitro natural cell-mediated activity against Salmonella typhimurium by intestinal and splenic lymphoid cells in mice.

In vitro natural anti-bacterial activity against Salmonella typhimurium by lymphocytes from Peyer's patches and spleens was assessed in several mouse strains. C3H/HeN and CBA/J mice, which are resistant to S. typhimurium infections, showed a natural anti-bacterial activity significantly higher than BALB/c, C57BL/10, C57BL/6 and C3H/HeJ mice, i.e. strains susceptible to the in vivo bacterial infection. In these susceptible strains and also in A/J mice, a significantly higher natural activity was observed in females compared to males. The sex control of natural anti-bacterial activity was further stressed by the fact that orchidectomy could induce a strong activity in low responder C57BL/10 male mice. With the exception of Beige mice, a low natural killer (NK) strain also with no natural activity against S. typhimurium in both sexes, the genetic distribution of natural anti-bacterial activity was extremely different from that of the NK activity. Thus, these results further stress the difference between natural anti-bacterial activity and NK cytotoxicity. Furthermore, our data establish a possible link, although with some exceptions, between in vivo susceptibility to S. typhimurium infections and in vitro natural activity against these bacteria.

Animals↗