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Biomedical subjects

H Kirchner

Publications and source records attributed to H Kirchner.

At least 379 records · Page 21Linked to original sources
PubMed1983

Herpes simplex virus type 1-induced interferon production and activation of natural killer cells in mice.

Cultures of peritoneal exudate cells (PEC) of non-immune C57BL/6 mice reacted to infectious herpes simplex virus type 1 (HSV), but not to non-infectious virions by producing interferon. Similarly, when the virus preparations were injected intraperitoneally (i.p.) and interferon was determined in the wash-out fluid, interferon could only be detected after injection of infectious HSV. All interferons were mixtures of interferon-alpha and -beta. The cell that produced interferon was not sensitive to anti-theta serum or anti-asialo-GM1 serum, it was retained on nylon wool columns and removed by plastic adherence. Silica treatment of PEC abolished HSV-induced interferon production whereas irradiation by 2000 R was without effect. Pure cultures of mouse T cells did not produce interferon when treated with infectious HSV whereas pure cultures of mouse bone marrow macrophages did produce interferon. Thus, we suggest that in PEC the cells which produced interferon were of the macrophage lineage. In further experiments we have analysed in vivo activation of natural killer (NK) cells in the peritoneal cavity of mice. Non-infectious virions were as effective as infectious HSV and doses of HSV too low to induce measurable titres of interferon caused a marked activation of NK cells.

Animals↗
PubMed1983

Neuropathogenicity of herpes simplex virus in mice: protection against lethal encephalitis by co-infection with a non-encephalitogenic strain.

Intraperitoneal infection of susceptible mice with an apathogenic herpes simplex virus type 1 (HSV-1) strain prevented the lethal outcome of a challenge infection with a pathogenic strain, even if the challenge preceded the protective infection. It was found that the protective inoculation blocks the initial replication of the challenge virus. In addition, intraperitoneal infection with the protective HSV-1 strain led to the induction of a refractory state in the central nervous system, resulting in resistance to direct intracranial infection with HSV-1. This state is also inducible locally by intracerebral inoculation of a non-replicating mutant virus. The results indicate that HSV-1 strains differing in neurovirulence may differ in the induction or the sensitivity to this protective effect. Experiments with non-replicating HSV-1 temperature-sensitive strains demonstrated that protection against lethal infection does not depend on replication or expression of late genes of the protective strain. Inoculation of animals with detergent-soluble extracts of infected cells or infected and u.v.-irradiated syngeneic cells protected the animals against co-infection with encephalitogenic challenge virus. The experiments define this protective effect as an antigen-induced-immediate host defence mechanism active within 24 h post-infection.

Animals↗
PubMed1983

Genetic variability of herpes simplex virus: development of a pathogenic variant during passaging of a nonpathogenic herpes simplex virus type 1 virus strain in mouse brain.

Herpes simplex virus type 1 ANG (HSV-1 ANG) is originally nonpathogenic for inbred mice upon intraperitoneal intravenous, or intravaginal inoculation. In contrast, mice died of encephalitis within 4 to 5 days after intracerebral inoculation with this strain. HSV-1 ANG was serially passaged in mouse brains. In two independent series, peripherally pathogenic virus variants had developed and accumulated in the virus progeny after 12 to 15 intracerebral passages. In mixed infections both nonpathogenic and pathogenic viruses replicated at the primary site of infection and spread to various organs. However, only the pathogenic phenotype could be recovered from the spinal cord and the brain. Comparison of the restriction enzyme cleavage patterns of pathogenic ANG and nonpathogenic ANG virus DNAs revealed distinct alterations in the S-segment (US) sequences bounded by coordinates 0.953 and 0.958 in the prototype orientation and by coordinates 0.862 to 0.867 in the IS orientation of the viral genome. However, it is not known whether these alterations are physiologically relevant to the observed changes in pathogenicity. When coinjected intraperitoneally at 50 to 100-fold excess, the nonpathogenic HSV-1 ANG protected mice against its own pathogenic variant as well as against other pathogenic HSV-1 strains. Pathogenic HSV-1 ANG proved to be genetically and phenotypically stable for at least 25 serial passages in tissue culture at either high or low multiplicity of infection.

Animals↗
PubMed1983

Replication of herpes simplex virus in human T lymphocytes.

The replication of herpes simplex virus (HSV) in cultures of human T lymphocytes was investigated. Virus replication occurred only in lymphocyte cultures prestimulated with mitogen. At least one of the factors responsible for this phenomenon is adsorption of the virus to the cells, which was 5 times less efficient in nonstimulated cells than in stimulated cultures. Growth of virus in infected cultures was restricted to lymphocytes of T origin. This was shown by successful infection of highly purified T-cell cultures and by virus replication in four continuous T-cell lines. No virus production was obtained in cultures of lymphocytes of other than T-cell origin. Virus titers in T-lymphocyte cultures reached 10(7) PFU/ml, which was a four log10 step increase over the input dose. Lymphocytes infected with a syn strain of HSV, HSV-ANG, induced polykaryocyte formation in the cultures and therefore generated a CPE visible by microscopic examination. Infection with syn+ strains of HSV (i.e., strains which do not cause cell fusion) did not lead to such phenomena. Not more than 1% of infected T cells was replicating HSV, as revealed by infectious center assays. In contrast, about 5% of these cells showed positive immunofluorescence with anti-HSV antibodies, indicating the presence of cells which express viral protein but do not actively produce infectious virus.

Antigens, Viral↗
PubMed1983

The autologous mixed lymphocyte reaction in patients with rheumatoid arthritis.

In patients with rheumatoid arthritis (RA) a significantly decreased autologous mixed lymphocyte reaction (AMLR) was observed which varied widely and did not correlate with disease activity, clinical course or treatment schedules. When supernatants of AMLR cultures were tested for the presence of soluble factors no differences were found in regard to the suppression of allogeneic and mitogen induced lymphocyte proliferation. Furthermore both test groups failed to produce detectable amounts of interferon during the course of the AMLR, in contrast to the allogeneic situation were both RA patients and normal controls exhibited a similar interferon activity in the culture supernatants.

Adult↗
PubMed1982

Rapid separation of T cell subpopulations with monoclonal antibodies and affinity chromatography.

A rapid method for isolation of highly enriched helper and suppressor T cell subsets and their corresponding helper and suppressor cell depleted cell populations is described. The method is based on the binding of monoclonal antibodies to helper and suppressor cells and subsequent affinity chromatography with covalently bound rabbit anti-mouse antibodies. As assessed by indirect immunofluorescence, purity of the enriched subpopulations exceeds 90%, whereas no contamination with helper or suppressor cells is detectable in populations depleted of the respective subsets. The cells isolated by this method show no functional defects in helper and suppressor assays and respond with increased DNA synthesis to stimulation with phytohemagglutinin (PHA) plus 2-mercaptoethanol (2-ME).

Animals↗
PubMed1982

Interferons and bacterial infections.

Viruses have been established initially as interferon inducers and interferons have been considered to be antiviral proteins only. By our article we wish to draw attention to two observations: a) bacteria and derivatives thereof also are inducing the production of interferon b) interferons activate a number of defense mechanisms that are of potential relevance in antibacterial resistance. These two observations are not new. However, we believe, they deserve renewed attention within the framework of the pleiotropism of interferon effects and of the complexity of antibacterial defense mechanisms.

Animals↗
PubMed1982

Heterogeneity of soluble T cell products. I. Precursor frequency and correlation analysis of cytotoxic and immune interferon (IFN-gamma)-producing spleen cells in the mouse.

In this study, the precursor frequency, relationship and activity of murine splenic cytotoxic and immune interferon (IFN-gamma)-producing cells has been determined. C57BL/6 spleen cells were activated by concanavalin A (Con A) and subsequently grown in microcultures under limiting dilution conditions. The progeny of cells plated in microcultures was divided and tested for (a) total cytotoxic activity on EL4 (H-2b) tumor target cells in the presence of Con A to nonspecifically attach the killer to the target cells, and (b) the quantity of IFN-gamma released by Con A stimulation. Cytotoxic T lymphocytes and IFN-gamma-producing cells were present in Con A-activated C57BL/6 spleen cells at a high frequency of approximately 1 out of 3 and 1 out of 2 cells, respectively. IFN-gamma could be released from both noncytotoxic and a large fraction of cytotoxic T cells and the cytotoxic activity was not necessarily associated with IFN-gamma release. In a few selected cultures with a progeny of cells plated at a low cell number (up to 10/well) very high IFN-gamma titers (greater than 10 000 U/ml) could be found. These results provide the first frequency estimate of IFN-producing cells and are discussed with respect to the physiological role of IFN-gamma release from T cells.

Animals↗
PubMed1982

Production of immune interferon is regulated by more than T cell subset: Lyt-1,2,3 and Qat-5 phenotypes of murine T lymphocytes involved in IFN-gamma production in primary and secondary mixed lymphocyte reaction.

Lymphocytes responsible for the production of IFN-gamma (immune interferon) in primary and secondary mixed lymphocyte reactions have been characterized with antisera specific for the Lyt-1,2,3 and Qat-5 alloantigens. A comparison was made between selected T cell subsets with respect to their ability to proliferate, generate cytolytic activity and produce IFN-gamma in response to H-2 alloantigens. The data indicate that (a) in primary mixed lymphocyte reactions, IFN-gamma is produced by Lyt-1+, Qat-5+ and by Lyt-123+, Qat-5+ T cells, (b) in secondary mixed lymphocyte reactions, an additional T cell subset, which is Lyt-23+, Qat-5-, participates in the generation of IFN-gamma and (c) the production of IFN-gamma does not correlate with either proliferation or the generation of cytotoxic lymphocytes.

Animals↗
PubMed1982

Production of high titers of interferon-gamma by prestimulated murine spleen cells.

Concanavalin A (Con A)-induced interferon-gamma (IFN-gamma) production by murine spleen cells prestimulated with Con A for different periods of time has been studied. Highest titers of antiviral activity were obtained by restimulation of cells that had been prestimulated with Con A for 3 days. These cells produced up to 30 times more IFN than freshly isolated spleen cells stimulated under the same conditions. In an effort to explain this rise in the capacity to produce IFN-gamma, the possibility that it was due to the inactivation of a suppressor cell was excluded. The addition of freshly isolated spleen cells at different concentrations to prestimulated cells did not affect subsequent Con A-induced IFN-gamma production. Separation of freshly isolated or prestimulated spleen cells by velocity sedimentation at unit gravity showed that in the latter case most of the IFN-gamma was produced by a population of large-sized cells not present in the former population. It was concluded from these experiments that prestimulation of spleen cells with Con A gives rise to a population of large-sized cells that produce, upon restimulation with the same mitogen, much higher titers of IFN-gamma than those obtained upon primary stimulation of small resting lymphocytes.

Animals↗
PubMed1982

Induction of interferon in murine bone marrow-derived macrophage cultures by 10-carboxymethyl-9-acridanone.

10-Carboxymethyl-9-acridanone (CMA) induced high titers of interferon (IFN) in murine leukocyte cultures. Thymocytes, lymph node, spleen and peritoneal exudate cells responded to CMA with IFN production. Pure macrophages derived from the bone marrow were the most efficient producers of CMA-induced IFN. The yields of IFN-alpha, beta in the macrophage supernatants depended on the concentration of the inducer and titers up to 3000 IU/ml were measured after exposure to the optimal dose (500 micrograms/ml). CMA was found to be the first low molecular weight compound that induced in vitro titers of IFN nearly as high as obtained after exposure to Newcastle disease virus, which is one of the most potent interferon inducers.

Acridines↗
PubMed1982

Experimental infection of inbred mice with herpes simplex virus. IV. Comparison of interferon production and natural killer cell activity in susceptible and resistant adult mice.

Inbred mouse strains differ in susceptibility to infection with herpes simplex virus type 1 or type 2 (HSV-1, HSV-2). In this study interferon production was tested in the peritoneal exudate of mice after intraperitoneal (i.p.) injection of HSV-1 or HSV-2. In HSV-resistant mice (C57 BL/6, C3 H/HeJ) high titers of interferon were already present 2 to 4 hours after injection. In comparison, less resistant mice (DBA/2, AKR) lacked this early response. There was no correlation between interferon titers and resistance at post-infection times later than twelve hours. At twelve hours, however, high titers of HSV were detected in the peritoneum of DBA/2 mice and significantly lower titers in C57 BL/6 mice. In a comparative analysis of eight different inbred mouse strains, again early (2 to 4 hours) interferon production was correlated to resistance. In assays of HSV-stimulated early (24 hours) NK cell responses not only the good interferon producer strains but also one of the less resistant low interferon producers (BALB/c) showed significant cytotoxic activities. Conversely, SJL mice that are very low in HSV-induced NK cell activity are resistant and show high early interferon responses at the local site.

Animals↗