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Biomedical subjects

R Zinkernagel

Publications and source records attributed to R Zinkernagel.

36 records · Page 2Linked to original sources
PubMed1993

CD4 negative mice as a model for immunodeficiency.

CD4 is a co-receptor required for T cell helper functions. A mouse strain without CD4 expression has been generated. These animals, surprisingly have a normal CTL response and reduced, but not absent, humoral responses. A new population of MHC class II restricted CD4-CD8-TcR alpha beta+ T cells has emerged which possess helper function potential. These findings have important implications on disease situations where CD4 cells are decreased or absent.

Animals↗
PubMed1993

Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes.

Tumour necrosis factor (TNF), jointly referring to TNF alpha and TNF beta, is a central mediator of immune and inflammatory responses; its activities are mediated by two distinct receptors, TNFR1 (p55) and TNFR2 (p75) (reviewed in refs 1-3). The cytoplasmic domains of the TNFRs are unrelated, suggesting that they link to different intracellular signalling pathways. Although most TNF responses have been assigned to one or the other of the TNF receptors (mostly TNFR1), there is no generally accepted model for the physiological role of the two receptor types. To investigate the role of TNFR1 in beneficial and detrimental activities of TNF, we generated TNFR1-deficient mice by gene targeting. We report here that mice homozygous for a disrupted Tnfr1 allele (Tnfr1(0)) are resistant to the lethal effect of low doses of lipopolysaccharide after sensitization with D-galactosamine, but remain sensitive to high doses of lipopolysaccharide. The increased susceptibility of Tnfr1(0)/Tnfr1(0) mutant mice to infection with the facultative intracellular bacterium Listeria monocytogenes indicates an essential role of TNF in nonspecific immunity.

Animals↗
PubMed1992

Kinetics of clonal deletion varies with tolerizing antigen.

In postnatal AKR/J mice (I-Ek, Mls-1a) potentially autoreactive T-cells bearing V beta 11+ or V beta 6+ TcR are present until day 4, rapidly decreasing thereafter. Clonal deletion of V beta 11+ and V beta 6+ T-cells shows equivalent kinetics and is complete after day 7 to 8. Analysis of transgenic mice expressing a TcR with double specificity for LCMV/H-2Db and for Mls-1a revealed that in mice congenically infected with lymphocytic choriomeningitis virus (LCMV) T-cells bearing the transgenic TcR were already deleted at birth, whereas in uninfected TcR-transgenic Mls-1a mice deletion was delayed. These findings document that the capacity of the thymus to induce tolerance by clonal deletion is already established at birth and that the kinetics of clonal deletion varies with tolerizing antigen.

Animals↗
PubMed1990

Characterization and immunological properties of influenza A virus nucleoprotein (NP): cell-associated NP isolated from infected cells or viral NP expressed by vaccinia recombinant virus do not confer protection.

A nucleoprotein (NP) preparation purified from the chorioallantoic membrane of chicken eggs infected with fowl plague virus (A/FPV/Rostock/34, H7N1) yielded, in addition to the commonly known 56K protein, a 42K component that could not be detected in virus particles. After testing with a series of NP-specific monoclonal antibodies it was found that some reacted with both proteins and others were bound only by the 56K protein. Among both types of NP-specific monoclonal antibodies only a limited number were bound to infected murine cells. Some antibodies bound to cells infected with a given subtype failed to react with the surface of cells infected with a different subtype. Binding was demonstrated by cellular ELISA, radioimmunoassay and immunofluorescence. The results indicate that only restricted antigenic domains of the native NP and perhaps NP fragments are exposed at the surface of infected murine cells. Additionally, the purified NP preparation was used to immunize mice in order to determine the protective capacity of cell-associated NP. In parallel, and as a relevant control, mice were immunized with a vaccinia virus recombinant containing the gene for NP prior to challenge with infectious virus. High levels of monospecific antibodies and a cytotoxic T cell activity was found in mice immunized with purified NP or infected with the vaccinia recombinant after secondary restimulation in vitro. After treatment with specific antibodies the cytotoxic cells were shown to be classical CD8+ cytotoxic T lymphocytes. Despite the elicitation of a humoral and a cellular immune response by the forms of NP employed mice were not protected from influenza virus infection.

Animals↗
PubMed1986

Astrocytes as antigen-presenting cells. Part II: Unlike H-2K-dependent cytotoxic T cells, H-2Ia-restricted T cells are only stimulated in the presence of interferon-gamma.

Various studies strongly suggest that astrocytes are potent immune-regulating cells. They can be activated to release prostaglandin E, interleukin-1- and interleukin-3-like factors. Cocultivation of antigen-specific T cell lines and astrocytes results in induction of Ia on astrocytes and antigen-specific proliferation of T cells. In the current study, astrocytes were found to be incapable of serving as stimulator cells when unprimed T lymphocytes were used as responders in syngeneic or allogeneic lymphocyte reactions. However, when interferon-gamma (IFN-gamma) was added, astrocytes became Ia positive and potent stimulators in both syngeneic or allogeneic lymphocyte responses. In the presence of IFN-gamma, astrocytes presented antigens to Ia-restricted T hybridoma cells; in contrast hapten was presented to Kb-restricted cytotoxic cloned T cells by astrocytes in the absence of IFN-gamma. Thus, cultured astrocytes do function directly as accessory cells in class I antigen-dependent T cell activation, whereas Ia induction by IFN-gamma is necessary to enable them to present antigen to class II antigen-restricted T cells.

Animals↗
PubMed1985

Natural killer cells vs cytotoxic T cells in the peripheral blood of virus-infected mice.

The cell-mediated immune response of mice against various enveloped RNA and DNA viruses expressed by immune lymphocytes from the spleen and the peripheral blood (PBL) were compared. PBL from mice of various strains infected with vaccinia virus, vesicular stomatitis virus (VSV), or lymphocytic choriomeningitis virus (LCMV) were tested on histocompatible or incompatible target cells infected with the homologous virus. PBL from immune mice showed clear H-2 restriction, but additionally, they expressed high natural killing (NK) activity on YAC-1 cells. The high NK-cytolytic activity of PBL on YAC-1 differed significantly from that expressed by splenic lymphocytes. In both lymphocyte populations lysis was detected as early as 1 day after infection; NK activity decreased in the spleen after day 4 post infection, whereas that of PBL persisted at high levels for up to 10 days after infection. Treatment of mice with anti-asialo GM1 in vivo abrogated NK activity in PBL effector cells tested in vitro. These results may explain some of the difficulties to observe MHC-restricted cytotoxic T cells in PBL from humans or primates during primary infections with virus.

Animals↗
PubMed1984

Immune response against vaccinia virus in rhesus monkeys: no evidence for primary MHC-restricted cytolytic T cells.

Rhesus monkeys were tested in vitro for their cellular immune response after infection with vaccinia virus, employing lymphocyte preparations from various lymphoid tissues. Although virus-infected target cells were lysed by lymphoid cells from immunized, but not from uninfected, rhesus monkeys, we could neither find evidence for MHC-restricted T cells nor for antibody-dependent cellular cytotoxicity. Kinetics of target cell lysis, the killing patterns of immune lymphocytes measured on syngeneic, allogeneic, and xenogeneic target cells, and the influence of protein A on cytotoxic activity in vitro suggest induction predominantly of natural killer cells in vivo which exhibit lytic activity on virus-infected target cells in vitro.

Animals↗
PubMed1978

Generation of virus-specific cytolytic activity in human peripheral lymphocytes after vaccination with vaccinia virus and measles virus.

Human peripheral blood lymphocytes (PBL) harvested after vaccination with vaccinia or measles virus showed a specific activity against virus-infected target cells. This activity peaked on day 7 and was specific for the target cells infected with the virus used for the vaccination. The cytotoxic activity was not related to HLA markers. The cells involved in the cytolytic process were lymphocytes bearing Fc receptors. In addition, the cytotoxic activity was abrogated by more than 90% by rabbit Fab'2 anti-human IgG. It is therefore likely that two subpopulations of lymphocytes are involved: an antibody-secreting cell providing specific antiviral antibody and an effector cell bearing Fc receptor (K cells). Finally, these experiments suggest that antibody-dependent cell cytotoxicity may play a major role in the recovery from virus infection in man.

Adult↗
PubMed1975

[Adherence of pathogenic Escherichia coli to epithelial cells isolated from the intestinal mucosa of the rabbit, inhibiting effect of hyperimmune bovine colostrum and of various carbohydrates (author's transl)].

In order to study the mode of action of a bovine anti-Escherichia coli lactoserum (BLS), we have used a new test measuring the adherence of pathogenic E. coli on epithelial cells isolated from the small intestine of rabbit. A mixed suspension of E. coli and of epithelial cells is incubated for 15 min and the number of bacteria adhering to the cells counted under the microscope. The BLS at a concentration of 3.5 mg/ml IgG is able to reduce this number by a factor of 3-5. After absorption of the BLS with formaldehyde-treated bacteria, this factor is smaller than 2. At a concentration of 5 mg/ml, D-mannose and alpha-methylmannoside are as efficient inhibitors of adherence as BLS; at the same concentration, L-mannose is ineffective. The cultures of E. coli strongly agglutinating guinea pig erythrocytes, adhere to a larger extent to the epithelial cells. The last two observations confirm the important role played by fimbriae for the adhesive properties of E. coli. The presence of fimbrial antibodies would partially explain the inhibiting effect of BLS on adherence.

Animals↗
PubMed1975

Fluorescent whitening agents in the environment.

An assessment of the ecological situation regarding the use of fluorescent whitening agents (FWAs) is given. Firstly a survey is made of the existing literature with references to the contributions on the subject in this EQS supplement volume, then the effects of waste water treatment with respect to the elimination of FWAs in the different stages of treatment are discussed. The final load of FWAs in receiving water is estimated. These figures are brought into relation with the actual content of receiving water residues of natural and manmade origins. The significance of the FWA load is discussed. All the arguments lead to the strong suggestion that these residues are finally metabolized by natural systems of elimination, so that no ecological risks exist when FWAs are properly used in the main fields of application, i.e. in the textile, paper and soap and detergent industry.

Animals↗
PubMedDate not supplied

Identical V beta T-cell receptor genes used in alloreactive cytotoxic and antigen plus I-A specific helper T cells.

T lymphocytes involved in the cellular immune response carry cell-surface receptors responsible for antigen and self recognition. This T-cell receptor molecule is a heterodimeric protein consisting of disulphide-linked alpha- and beta-chains with variable (V) and constant (C) regions. Several complementary DNA and genomic DNA clones have been isolated and characterized. These analyses showed that the genomic arrangement and rearrangement of T-cell receptor genes using VT, diversity (DT), joining (JT) and CT gene segments is very similar to the structure of the known immunoglobulin genes. We have isolated two cDNA clones from an allospecific cytotoxic T cell, one of which shows a productive V beta-J beta-C beta 1 rearrangement without an intervening D beta segment. This V beta gene segment is identical to the V beta gene expressed in a helper T-cell clone specific for chicken red blood cells and H-21. The other clone carries the C beta 2 gene of the T-cell receptor, but the C beta 2 sequence is preceded by a DNA sequence that does not show any similarity to V beta or J beta sequences.

Animals↗