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Biomedical subjects

A Tagliabue

Publications and source records attributed to A Tagliabue.

At least 91 records · Page 5Linked to original sources
PubMed1988

Human T-cell immunity against Bordetella pertussis analyzed at clonal level.

Cloned peripheral blood T lymphocytes from an immune donor were grown in interleukin 2 and tested for proliferation in response to inactivated Bordetella species (B. pertussis, B. parapertussis and B. bronchiseptica) and mutants deficient for the expression of virulence-associated antigens. All the T-cell clones obtained were CD4+8- and recognized specifically the Bordetella antigens when presented by autologous B cells. On the basis of the responsiveness to the whole inactivated bacteria, it was possible to cluster the twelve clones obtained into four groups with the following specificity: 1) filamentous hemagglutinin (FHA): 2) B. pertussis specific antigens; 3) virulence-associated Bordetella specific antigens; 4) non-virulence-associated Bordetella specific antigens. Employing two new B. pertussis deletion mutants, clone 6 (representative of cluster 1), was found to recognize the C-terminus of FHA. Furthermore, 3 out of 4 clones of cluster 3 were specifically stimulated by the soluble 69,000 MW protein from the outer membrane of B. pertussis. Surprisingly, none of the twelve clones obtained by stimulation in vitro with whole inactivated bacteria recognized PT. Thus, PT does not seem to be the most representative antigen on the whole inactivated bacteria. However, when a new generation of clones was obtained using soluble PT as the in vitro stimulus, it was observed that 11 clones of this group recognized this antigen. Furthermore, the majority of them was against the subunit S1 of PT. Therefore, we can conclude that a T-cell memory against PT exists in a donor who has had pertussis several years before. In conclusion, these results provide useful information in the attempt to obtain a simplified acellular vaccine for whooping cough.

Antigens, Bacterial↗
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

Interferons inhibit LTC4 production in murine macrophages.

Mouse resident peritoneal macrophages (M phi) produce the highly bioactive eicosanoid LTC4 when stimulated in vitro with zymosan or with the calcium ionophore A23187. This production was dramatically inhibited in M phi pre-exposed to IFN-alpha, IFN-beta, or IFN-gamma. Although all IFN were able to decrease the availability in M phi of the LTC4 precursor AA, this decrease was not the only cause of the IFN-induced inhibition of LTC4. In fact, further analysis of the different steps of the LTC4 biosynthetic pathway revealed that IFN-gamma could inhibit the formation of LTA4, thus of its derivatives LTC4 and LTB4, possibly acting at the level of the enzyme LTA4-synthetase. In contrast, IFN-alpha and IFN-beta only depressed the ability of M phi to metabolize AA into LTC4, leaving unaltered the synthesis of LTB4. However, IFN-alpha and IFN-beta did not influence directly the activity of any of the enzymes involved in LTC4 biosynthesis, indicating that they may act through some indirect, as yet unidentified regulatory mechanism. These data suggest that IFN-alpha and IFN-beta and, in different situations, IFN-gamma can be potentially useful in vivo in antagonizing localized anaphylactic or inflammatory reactions.

Animals↗
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

A short synthetic peptide fragment of human interleukin 1 with immunostimulatory but not inflammatory activity.

Short peptide fragments of human and murine interleukin 1 (IL 1) were synthesized on the basis of their predicted exposure on the surface of the molecule in an attempt to identify the minimal structure responsible for the immunostimulatory activity of IL 1. One of these peptides, a fragment of nine residues of human IL 1 beta (VQGEESNDK, fragment 163-171), showed high T cell activation capacity, as judged by its ability to stimulate murine thymocyte proliferation and to potently induce interleukin 2 production in spleen cells. On the other hand, the 163-171 peptide was devoid of prostaglandin-inducing capacity in vitro and pyrogenic activity in vivo, two inflammatory features peculiar to the entire hu IL 1 beta molecule. Thus we propose that this peptide may represent one of the portions of hu IL 1 beta responsible for its immunostimulatory capacity.

Amino Acid Sequence↗
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↗
PubMed1986

Anti-inflammatory activity of IFN-beta in carrageenan-induced pleurisy in the mouse.

The effect of IFN-beta on the development of the inflammatory reaction was studied in an experimental animal model, carrageenan-induced pleurisy in the mouse. Intrapleural inoculation of IFN-beta at the same time as carrageenan administration inhibited both migration of inflammatory cells and exudate formation in the pleural cavity in a dose-dependent fashion. Similarly, IFN-beta decreased the presence of the arachidonate metabolites PGI2, TXA2 and PGE2 (highly active molecules involved in the regulation of the inflammatory reaction) in inflammatory exudates. A marked inhibition of the inflammatory response to carrageenan was also evident when IFN-beta was administered several hours after the inflammatory challenge. In contrast, administration of IFN-gamma did not modify significantly any of the inflammatory parameters considered.

Animals↗
PubMed1985

Natural antiviral activity of mouse macrophages against encephalomyocarditis virus.

Resident mouse peritoneal cells (PC) express a significant antiviral activity against encephalomyocarditis virus (EMCV) in vitro, as judged by decreased virus yield from infected mouse embryo fibroblasts (MEF). This natural antiviral activity of PC was not due either to enhanced lysis of virus-infected cells, as these were protected from lysis rather than destructed by PC, or to interferon (IFN) production, as no direct correlation between IFN and anti-EMCV activity was found. Among PC, macrophages (M phi) appear to be responsible for the anti-EMCV activity, which was indeed attributable to a Thy 1.2-negative, adherent mononuclear cell. Moreover, M phi-defective C3H/HeJ mice showed a significant impairment of anti-EMCV activity, whereas M phi of mice defective for natural killer (NK) activity (bg/bg, SJL/J) or for mature T cells (nu/nu) possessed an intact antiviral capacity.

Animals↗
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↗