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Biomedical subjects

H Kirchner

Publications and source records attributed to H Kirchner.

At least 451 records · Page 25Linked to original sources

Protection of mice against viral infection by Corynebacterium parvum and Bordetella pertussis.

Mice could be significantly protected against infection with herpes simplex virus (HSV) by i.p. or i.v. injection of killed Corynebacterium parvum 7 days before infection. This protection was seen in inbred strains of mice with a different degree of sensitivity to HSV and after both i.p. and i.v. infection. Resistant mice immunosuppressed by X-irradiation and showing an increased susceptibility to HSV could also be protected by a previous injection of C. parvum. Elevated levels of interferon were demonstrated in the serum of mice injected with C. parvum 5 to 12 days previously. Four different strains of anaerobic coryneforms were compared and only those which were able to induce a systemic activation of the lymphoreticular system (as reflected by splenomegaly) protected against HSV infection. Protection against HSV-infection could also be demonstrated by using killed Bordetella pertussis. C. parvum also protected against Semliki Forest virus infection in two different strains of mice.

Animals↗

In vitro mitogenic stimulation of murine spleen cells by herpes simplex virus.

Spleen cells of B6 mice not previously immunized were induced to DNA synthesis by supernatants from HSV-infected tissue culture. The stimulatory principle could be passed through a 45-micrometer filter and sedimented at 100,000 x G. It was abolished by UV light, heating at 56 degrees C, and by an anti-HSV serum. The possibility that the observed stimulation was caused by LPS was therefore excluded, and there was a-so no indication of mycoplasma contamination. Partial purification of spleen cells from macrophages resulted in an increased stimulation by HSV. From experiments with nylon columns, anti-theta antibody, and nude mice it was concluded that HSV acted as a B cell mitogen. Strains of both HSV types 1 and 2 were stimulatory for B6 spleen cells. Of nine freshly isolated HSV strains with identical passage history (twice in HEF) four were strongly stimulatory, three showed a moderate stimulation, and two did not stimulate. Spleen cells from A/J and DBA/2 mice were stimulated to the same extent by HSV (WAL) as spleen cells from B6 mice. No viral replication was demonstrable in B6 spleen cell cultures stimulated for DNA synthesis by HSV. Thus our study demonstrates induction of cellular DNA synthesis in B lymphocytes by HSV which is abolished by inactivation of the virus.

Animals↗

Differences in susceptibility to herpes simplex virus infection of inbred strains of mice.

Marked differences were observed between the susceptibility of adult C57BL/6 and DBA/2 mice to infection with HSV-1. These differences were seen after various infection schedules but were most marked after i.p. infection. A significant difference between the LD50 after i.p. infection was also observed between LPS-resistant C3H/HeJ and the closely related LPS-sensitive C3HeB/FeJ mice. Injection of LPS significantly increased the LD50 after i.p. infection with HSV in C57BL/6 or C3H/HeJ mice but not in C3HeB/FeJ mice. In vitro pretreatment with LPS was necessary to demonstrate replication of HSV in mouse spleen-cell cultures. Such replication could be demonstrated in cultures of DBA/2 and C3HeB/FeJ but not in C57BL/6 or C3H/HeJ mice.

Animals↗

Monocyte-dependent stimulation of human T cells by zinc.

Subpopulations of human peripheral blood leucocytes were isolated by nylon filtration or E-rosette separation and tested for functional activity. As shown previously, zinc ions induce DNA synthesis in unfractionated lymphocyte cultures. E-rosette-forming cells (E-RFC), obtained either by nylon wool filtration or E-rosette separation, responded well to PHA but showed only low levels of proliferative reactivity to zinc and Con A. These dminished responses could be completely restored by the addition of small numbers of autologous, mitomycin-treated monocytes; further experiments suggested that a monocyte-derived soluble factor can substitute for monocytes in this function. B lymphocyte-enriched cell populations, containing less than 1% E-RFC, did not respond to zinc and showed only marginal reactivity to PHA and Con A.

Concanavalin A↗

Interferon production and lymphocyte stimulation in human leucocyte cultures stimulated by Corynebacterium parvum.

Killed C. parvum organisms stimulated a lymphoproliferative response in human peripheral leucocyte cultures of both adult and cord blood origin. They also induced high titres of interferon in cultures of adult leucocytes, but there was no correlation between the degree of lymphocyte stimulation and of interferon production. A considerable variability between donors was seen in both assays. The amount of interferon produced in C. parvum-stimulated cultures was considerably higher than that stimulated by the T-cell mitogens PHA and Con A and that induced by LPS. The anti-viral protein induced by C. parvum fulfilled the criteria of interferon and appeared to represent type II interferon.

Concanavalin A↗

Protection against herpes simplex virus infection in mice by Corynebacterium parvum.

Corynebacterium parvum administered in mice prior to herpes simplex virus (HSV) infection significantly protected them against lethal encephalitis. This was seen both with a mouse strain highly susceptible to HSV and with one relatively resistant to HSV. Mice immunosuppressed by cyclophosphamide and showing an increased mortality after HSV infection were also protected by C. parvum pretreatment. However, C. parvum given simultaneously with or after HSV infection did not exert a therapeutic effect.

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Effect of A. laidlawii on murine and human lymphocyte cultures.

Heat-inactivated A. laidlawii (AL) was found to be a potent mitogen for mouse spleen cells. Spleen cells from homozygous nude mice and spleen cells treated with anti-theta serum and complement responded as well as their respective controls, indicating that AL represented a B-cell mitogen for mouse spleen cells. Spleen cells from LPS-unresponsive C3H/Hej mice responded well to AL. The peripheral blood leucocytes from unselected human donors were also stimulated by AL, which appeared to represent a T-cell mitogen for human leucocytes. However, the possibility that it acted as a specific antigen could not be excluded. Attention was drawn to the possibility that the presence of mycoplasma might considerably affect the results of tests where tissue-culture cells or derivatives thereof are added to leucocyte cultures.

Acholeplasma laidlawii↗

Suppressor cells in tumor bearing mice and rats.

Suppressor macrophages in spleens of tumor bearing mice and rats were found to inhibit "in vitro" reactivity of lymphocytes to T and B cell mitogens and to allogeneic cells in the mixed lymphocyte tumor cell interaction and the "in vitro" generation of secondary cytotoxic effector cells. We propose that similar suppressor cells may play an important role in the general immunosuppression of tumor bearing hosts and in the inability of tumor bearing hosts to effectively reject the tumor.

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Mixed lymphocyte/tumor-cell interaction in a murine sarcoma virus (Moloney)-induced tumor system. Comparison between lymphoproliferation and lymphocyte cytotoxicity.

Studies of the MLTI were performed in a primary MSV-induced tumor system. Reactivity against mitomycin-C-treated RBL-5 cells could be detected during a limited period at about 14 days after virus injection. The degree of reactivity of MSV 14 spleen cells was quite variable; stimulation indices ranged from 2.2 to 9.4. Activity in the MLTI appeared to a great extent to be dependent on T-lymphocytes. A relatively broad spectrum of specificity was demonstrated in experiments using additional stimulating cells besides RBL-5. The kinetics of the MLTI correlated well with the kinetics of the primary cytotoxic response in the CRA against RBL-5 cells. However, positive results in the in vivo and in vitro secondary cytotoxicity assays could be detected between 21 and 100 days after MSV injection when the MLTI was negative. Transplantation resistance against challenge with RBL-5 tumor cells also persists for a long time after MSV inoculation. Our data therefore indicate that the MLTI, in contrast to the secondary cytotoxicity assays, does not correlate well with the status of in vivo immunity.

Animals↗

Inhibition of cell-mediated cytotoxicity against tumor-associated antigens by suppressor cells from tumor-bearing mice.

Spleen cells from mice bearing primary tumours induced by Moloney strain of murine sarcoma virus (M-MuSV) strongly inhibited the in vitro generation of specific secondary cell-mediated cytotoxic response of spleen cells from M-MusV regressor mice. These suppressor cells were resistant to treatment with anti-theta serum and complement or to X-irradiation. It appeared that suppressor cells may have had a role in limiting the host's immune response against tumor growth.

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