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Biomedical subjects

H Kirchner

Publications and source records attributed to H Kirchner.

At least 397 records · Page 22Linked to original sources
PubMed1982

A whole-blood technique for testing production of human interferon by leukocytes.

Interferon production was studied in mixtures of whole blood of healthy adults with tissue culture medium. There was no need to supplement the system with additional foreign serum and even the autologous serum and even the autologous serum could be removed by washing in serum-free medium with-out impairment of interferon production. Heparinized blood samples could be stored in the refrigerator overnight before performing the assay. In this test, production of interferon gamma was observed in response to phytohemagglutinin, concanavalin A, pokeweed mitogen, staphylococcal enterotoxin A, and to OKT-3, a monoclonal anti-T cell antibody. Production of interferon alpha was observed when viruses were used as inducers. Our experiments show that in the whole-blood assay the responses to several inducers of different types of interferons may be readily monitored under serum-free conditions. We believe that this test will be of value for testing large numbers of normal individuals (for investigations of the genetics of interferon production) or of patients with a variety of diseases.

Antilymphocyte Serum↗
PubMed1982

Modulation by cyclosporin A of murine natural resistance against herpes simplex virus infection. II. Influence on the HSV-induced natural killer cell responses, macrophage activities and interferon levels.

Cyclosporin A (CyA) interfered locally at the site of injection with several resistance functions which are of potential importance in experimental herpes simplex virus (HSV) infections of mice. HSV-induced stimulation of macrophage phagocytosis was reduced by CyA when the mice were infected 5 days before the assay. The in vitro replication of the virus in macrophages, however, was enhanced. Natural killer (NK) cell response were severely impaired. To some extent this could be attribute to the induction of suppressive macrophages by the drug treatment. Interferon levels induced by HSV were not diminished but rather enhanced in some experiments. Inhibitory effects ceased after termination of CyA treatment and could be prevented by presensitization of the mice with attenuated HSV type 2.

Animals↗
PubMed1982

Induction of interferon by mycoplasmas in mouse spleen cell cultures.

Interferon production in cocultures between lymphoma cells and lymphocytes was previously found to be caused by mycoplasma contamination of the tumor cells. Here we have shown that M. arginini caused interferon production in spleen cells of C57BL/6 mice. The producer cell in spleen cell cultures was insensitive to treatment with anti-theta serum plus complement and it was present in spleen cell cultures of homozygous nude mice. Macrophage depletion did not adversely affect interferon production whereas interferon production was abolished in cultures of cells obtained after passage through nylon wool columns. Collectively, these data suggest, but cannot definitively prove that interferon is produced by B cells. By the use of specific antisera it was found that by all probability the interferon produced represented interferon alpha.

Animals↗
PubMed1982

The role of interferon in the resistance of C57BL/6 mice to various doses of herpes simplex virus type 1.

C57BL/6 (B6) mice are relatively resistant to infection with herpes simplex virus type 1 (HSV-1). Paradoxically, B6 mice were resistant to 250 LD50 (50% lethal dose) of HSV-1 but were killed by 25 or 2.5 LD50 of HSV-1 injected intraperitoneally. At the injection site 250 LD50 of virus induced high titers of interferon (IFN) (greater than 1,000 international units) that reached maximal levels 2-4 hr after inoculation, whereas 25 or 2.5 LD50 of HSV-1 generated only borderline levels of IFN (15-40 international units). Simultaneous inoculation of 250 LD50 of HSV-1 and antiserum to mouse IFN (MuIFN) rendered B6 mice susceptible to infection; however, treatment with antiserum to MuIFN did not increase susceptibility to 1 LD50 of virus. Injections of MuIFN given 2 hr before and 2 hr after inoculation with virus protected B6 mice against 25 LD50 of virus. Thus, endogenous IFN induced after injection with 250 LD50 of HSV-1 protects B6 mice, whereas low doses of virus kill the animals because they do not generate a detectable IFN response at the infection site.

Animals↗
PubMed1982

Production of high titres of interferon-gamma by cells derived from short-term cultures of murine spleen leukocytes in T-cell growth factor-conditioned medium.

Short-term culture of activated murine spleen cells in T-cell growth factor-conditioned medium resulted in a cell population that produced high titres of interferon-gamma in response to the T-cell mitogen concanavalin A. Compared to interferon-gamma production by freshly isolated spleen cells in response to the same mitogen, titres were 10 to 20 times higher at all cell densities tested. Furthermore, the minimal cell density at which interferon-gamma production could be detected was significantly lower. The mitogen dose required for optimal interferon induction in this system was higher than in conventional spleen cell cultures.

Animals↗
PubMed1982

Experimental infection of inbred mice with herpes simplex virus. III. Comparison between newborn and adult C57BL/6 mice.

We have previously shown that adult C57BL/6 mice are relatively resistant to intraperitoneal (i.p.) infection with herpes simplex virus type 1 (HSV-1). Here we show that newborn mice of the strain C57BL/6 are highly susceptible to i.p. infection with HSV-1. Newborn C57BL/6 mice, in contrast to adult mice, did not develop natural killer cell activity in the peritoneal cavity 24 h after i.p injection of HSV-1, and showed only minimal titres of interferon in the peritoneal fluid after 4 h. After 24 h the peritoneal fluid of newborn mice contained high amounts of interferon and high titres of HSV-1. In contrast, the virus titres in the peritoneal cavity of adult mice were significantly lower. It is suggested that the early titres of interferon at the infection site that are observed in adult, resistant C57BL/6 mice but not in susceptible, newborn mice play a decisive role in resistance.

Aging↗
PubMed1982

An X-linked locus influences the amount of circulating interferon induced in the mouse by herpes simplex virus type 1.

Production of circulating interferon (IFN) was measured in inbred mouse strains following intravenous injection of herpes simplex virus type 1 (HSV-1). IFN titres reached maximal levels 2 to 3 h after injection of virus and a 10-fold difference was found between C57BL/6 mice and BALB/c, as high and low producers respectively. Mendelian analysis revealed that HSV-induced IFN production is governed by several loci, one of which is X-linked. The strain distribution pattern obtained from results in recombinant inbred lines and the results obtained in the congenic B6-C-H-28c-If-1(1) strain furthermore indicated an absence of close linkage to If-1. It is concluded that the levels of HSV-induced early IFN production are influenced by several autosomal loci and one X-linked locus.

Animals↗
PubMed1982

Activation of natural killer cells and induction of interferon after injection of mouse hepatitis virus type 3 in mice.

High levels of natural killer (NK) cell activity and high titers of interferon were observed in the peritoneal exudate of C57BL/6 mice 20 to 50 h after injection of mouse hepatitis virus type 3 (MHV3) but not during the first 10 h after infection. C57BL/6 mice were susceptible to MHV3 infection and showed high titers of MHV3 in the peritoneal exudate 48 h after infection. A/J mice, in contrast, were resistant to the dose that killed 100% of the C57BL/6 mice (10 macrophage-infecting doses) and showed considerably lower virus titers than those shown by C57BL/6 mice. NK cell activity and interferon titers were significantly lower in the peritoneal exudate of A/J mice than in that of C57BL/6 mice. Serum interferon titers were also lower in A/J mice. Thus, our data show an inverse relationship between resistance and the levels of these two parameters. The data suggest that, in contrast to the situation observed with certain herpesviruses, interferon and NK cells may not be of overwhelming importance in the defense of mice against MHV3.

Animals↗
PubMed1981

Hodgkin and sternberg-reed cell antigen(s) detected by an antiserum to a cell line (L428) derived from Hodgkin's disease.

Antisera to the cell line L428, derived from Hodgkin's disease, were raised in rabbits by injecting L428 cells intravenously and subcutaneously. The anti-L428 cell serum that did not react with HLA-DR was absorbed with tonsil cell plus acute myeloid leukemia cells or tonsil cells plus neutrophils, monocytes, and blood lymphocytes. Then it was tested for its ability to discriminate between L428 cells, Hodgkin and Sternberg-Reed cells, and various other cells. It was found that the anti L428 cell serum absorbed with tonsil cells plus acute myeloid leukemia cells stained only L428 cells, Hodgkin and Sternberg-Reed cells, and neutrophils. The anti L428 cell serum absorbed with tonsil cell plus neutrophils, monocytes, and blood lymphocytes reacted with L428 cells and Hodgkin and sternberg-Reed cells from 13 cases of Hodgkin's disease. It did not react with any other cell type present in the blood or in lymphoid tissue or with cells from five cases of non-Hodgkin's lymphoma. The absorbed anti-L428 cell serum also failed to stain Daudi and HRIK cell line cells. We conclude that the anti-L428 cell serum defines an antigen that is apparently restricted in expression to L428 cells and Hodgkin and Sternberg-Reed cells. This is a strong indication that the L428 cell line cells are derived from Hodgkin and Sternberg-Reed cells.

Antigens, Neoplasm↗
PubMed1981

Production of immune interferon by murine T-cell clones from long-term cultures.

Production of leukocyte interferon (IFN-alpha) and fibroblast interferon (IFN-beta) can be induced by a variety of agents but immune interferon, IFN-gamma, is only obtained when lymphoid cells are stimulated by specific antigens, allo-antigens or T-cell mitogens. Moreover, in bulk cultures, only small quantities of IFN-gamma are produced. The type of cell producing IFN-gamma has not been unambiguously defined and so we set out to determine whether a pure T-cell population could produce it, exploiting the knowledge that T cells can be maintained indefinitely in tissue culture by the addition of T-cell growth factors. Although not all T cells can found long-term cultures of this kind, cultures of antigen-specific helper, suppressor and killer T cells have been obtained in this way. We now describe the production of substantial amounts of INF-gamma when some (but not all) murine T-cell clones derived from such cultures are stimulated by either concanavalin A (Con A) or phytohaemagglutinin (PHA).

Animals↗
PubMed1981

Immunohistological analysis of Hodgkin's and Sternberg-reed cells: detection of a new antigen and evidence for selective IgG uptake in the absence of B cell, T cell and histiocytic markers.

To help clarify the origin and nature of Hodgkin's (H) and Sternberg-Reed (SR) cells, three different sets of experiments were performed. First, it was shown that cytoplasmic gamma, kappa, lambda occur not only in H and SR cells, but also in polymorphic tumor cells of epithelial, neurogenic, and lymphoid origin. Furthermore, human IgG that was injected i.v. into rats penetrated many rat liver cells, whereas injected human alpha 1-antitrypsin did not. Second, staining of frozen sections revealed that H and SR cells lack surface immunoglobulin and peripheral T-cell antigen. Third, an antiserum raised against the L 428 cell line (derived from Hodgkin's disease) and absorbed with human serum and normal cells did not react with any cells of tonsil tissue (lymphoid cells, histiocytes, and interdigitating reticulum cells), whereas it reacted strongly with the L 428 cell line cells and with H and SR cells of 10 different cases. In all ten cases, the antiserum stained the surface of H and SR cells; in two cases, it also stained the nucleoli and some chromatin spots in H and SR cells. The results obtained in these experiments indicate that H and SR cells are not closely related to lymphoid cells, histiocytes, or interdigitating reticulum cells. The findings also suggest that H and SR cells express one or more antigens that have not yet been detected on or in normal cells.

Animals↗
PubMed1981

[Epstein-Barr virus infection in the development of human tumors].

The Epstein-Barr Virus (EBV) is the only infectious agent for which a close association with human malignant tumors has been clearly demonstrated. These tumors are one type of nasopharyngeal carcinoma which is frequent in parts of East Asia and the Burkitt lymphoma which predominantly occurs in parts of Africa and New Guinea. Nonetheless, the EBV is the causative agent of infectious mononucleosis (IM), a benign, self-limiting lymphoproliferative disease of adolescents. The major difference between the countries in which the EBV-induced tumors occur and those in which IM occurs is the late primary EBV infection in the latter, whereas primary infection with EBV occurs in the first year of life in the former. All theories of viral carcinogenesis have to explain the long latency period between primary infection and tumor growth and how an ubiquitous virus may be oncogenic. Thus, invariably, one has to assume a role of cofactors, which may be of cytogenetic nature or may be represented by additional infections or by chemical agents. Since most modern theories of carcinogenesis consider a multi-step development of tumors, the theory that infection with an ubiquitous virus at the right time of life represents one step to carcinogenesis seems to be tenable.

Adolescent↗
PubMed1981

Protectivity of herpes simplex virus antigens: studies in mice on the adjuvant effect of PICLC and on the dependence of protection on T cell competence.

The efficacy of a herpes simplex virus type 1 (HSV-1) envelope antigen (EAG) preparation against HSV infection was studied in T cell competent and T cell deficient mice. Immuno-competent mice were successfully protected against herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) infection when immunized 2 weeks prior to this infection with a heat-inactivated whole virus preparation or a HSV-1 envelope antigen (HSV-1 EAG) preparation. Since HSV-1 EAG was considerably less effective than the whole virus preparation, a poly.riboinosinic-poly.ribocytidylic acid complex with poly-L-lysine and carboxymethylcellulose (PICLC) was used as adjuvant. Immunization with HSV-1 EAG plus PICLC resulted in a pronounced increase of this protection rate as compared with that obtained after immunization solely with HSV-1 EAG. PICLC alone, however, offered no protection when given 2 weeks before challenge. In T cell deficient nu/nu mice no protection was achieved with HSV-1 EAG while their T cell competent, heterozygous littermates were protected. From these results it may be concluded that T cell competence is a prerequisite for establishing a protective immunity against HSV infection after immunization with HSV-1 EAG.

Adjuvants, Immunologic↗
PubMed1981

Characteristics of alloantigens and cellular mechanisms responsible for gamma-interferon production in primary murine MLC.

We have investigated in primary murine MLC alloantigen differences and characteristics of responding cells responsible for gamma-IFN production. Differences at K, D, or I-S-G regions stimulate gamma-IFN release, though higher levels of production have been observed with differences at I-S-G regions. On the other hand, when mice differing in their minor histocompatibility antigens, notably at the MIs locus, were tested, gamma-IFN production took place even between strain combinations not displaying lymphocyte proliferation. Lastly, using different cell depletion techniques, we demonstrate that T-lymphocytes are the cells producing gamma-IFN upon stimulation with alloantigens. These findings show that T lymphocytes can recognize alloantigens by releasing gamma-IFN even without displaying proliferation.

Animals↗
PubMed1981

Protection of mice by an apathogenic strain HSV-1 against lethal infection by a pathogenic strain of HSV-1.

DBA/2 and C57BL/6 mice were infected intraperitoneally with two different strains of herpes simplex virus type 1, HSV-1 ANG and HSV-1 WAL. Unlike HSV-1 WAL, HSV-1 ANG was apathogenic by this mode of infection. Furthermore, infection with HSV-1 ANG protected mice of both inbred strains against infections with lethal doses of pathogenic HSV-1 WAL. This protection was observed when the apathogenic virus was given with the pathogenic virus or 4 to 24 h before it.

Animals↗