Biomedical subjects

K Bro-Jorgensen

Publications and source records attributed to K Bro-Jorgensen.

17 recordsLinked to original sources

PubMed1977

Changes in hemopoiesis during the course of acute LCM virus infection in mice.

Although severe hematologic and immunologic disorders occur in several viral infections, insight into the mechanisms by which viruses may affect hemopoietic tissues is poor. The previous demonstration of distinct immunohemopoietic lesions in mice with acute lymphocytic choriomeningitis (LCM) virus infection has led us to investigate the function of hemopoietic precursor cells in the course of this experimental infection. During the first week of infection, there was profound suppression of pluripotential stem cell (CFU) and in vitro colony-forming cell (CFU) compartments, and of 59Fe uptake into hemopoietic tissues. During the same period, we found enhanced activity of colony-stimulating factor, lack of responsiveness to erythropoietin, and appreciable titers of interferon in blood and spleen. After day 10 post infection, there was a striking increase in CFU and 59Fe uptake confined to spleen and blood. Restoration of bone marrow, however, was markedly delayed. With reference to recent studies on interferon, and the findings in mice with persistent LCM virus infection, we suggest that interferon may be the comprehensive suppressor of the hemopoietic precursor cells in the first stage of acute LCM virus infection, and that these cells in the recovery period are directed preferentially into erythropoiesis.

Acute Disease↗

PubMed1975

Transient impaired cell-mediated tumor immunity after acute infection with lymphocytic choriomeningitis virus.

Intraperitoneal injection of nononcogenic lymphocytic choriomeningitis (LCM) virus in adult C3H mice causes a symptomless infection but stimulates specific cell-mediated and humoral immune responses. However, median survival time of virus-infected mice inoculated with syngeneic tumor cells was significantly shortened, and growth of semiallogeneic tumors was significantly enhanced. Cell-mediated cytotoxicity measured as chromium-51 release from labeled tumor cells was significantly suppressed but was recovered within 55 days after infection. The suppressed immune responsiveness could be conferreo on a normal spleen cell population when activated in virus-infected recipients. Chronically LCM virus-infected mice showed an unimpaired cell-mediated immune response to tumor allografts.

Animals↗

PubMed1975

T lymphocyte function as the principal target of lymphocytic choriomeningitis virus-induced immunosuppression.

Plaque-forming cell responses against sheep erythrocytes, Escherichia coli lipopolysaccharide, pneumococcal polysaccharide, and polyvinylpyrrolidone were examined in mice infected with lymphocytic choriomeningitis virus. A 92 to 96 percent reduction of the thymus-dependent anti-sheep erythrocyte responses was observed 2 to 4 weeks after infection. However, the thymus-independent responses against the three other antigens were close to normal at all stages of the infetion. Studies on allograft immunity of infected C3H mice against DBA/2 mastocytoma cells revealed a severe suppression of the T cell-mediated cytotoxic response which was temporally related to the impaired humoral responsiveness against sheep erythrocytes. The capacity of spleen cells from infected mice to restore immune responsiveness of lethally irradiated recipients against sheep erythrocytes was significantly reduced. The adoptive responses, however, were clearly improved when normal thymus cells were added to the inferior spleen cells. Moreover, it appeared that the spleen cells from immunosuppressed donor mice could not confer suppression to normal lymphoid cells. The presented findings are consistent with the assumption that a numeric deficiency of T cells, or cells belonging to some T cell subpopulation, is the primary cause of lymphocytic choriomeningitis virus-induced immunosuppression.

Animals↗

PubMed1975

The activity of T and B lymphocytes in immunity and tolerance to the lymphocytic choriomeningitis virus in mice.

Treatment with anti-theta serum and the Wigzell column technique for cell separation was employed to study the separate functions of the B and T lymphocytes in the late states of immunity to the LCM virus in mice. The cell preparations examined were mixtures of spleen and lymph node cells from immune mice. The results revealed that the anti-viral effect of such cells after transfer to virus carriers was unimpaired in T cell-enriched and B cell-deprived cell preparations. The anti-viral effect was also retained in cell preparations deprived so much of B cells that no antibody was produced in the virus carrier mice receiving transplants of these cells. The results strongly indicate that the anti-viral effect of late immune cells is not only T cell-dependent but that it is also mediated solely by T cells and, moreover, that antibodies have no or very little influence on the virus elimination. The observation that antibody production could be caused neither by column-passed cells nor by anti-theta serum-treated cells, but was obtained by mixtures of these cells, demonstrates that co-operation between T and B cells is crucial for the LCM antibody response. Accordingly, the convincing demonstration of the absence in the persistent virus carriers of cells which, in respect of antibody production, are able to co-operate either with column-passed or with anti-theta serum-treated immune cells, implies that such animals are extremely deficient as regards immune function of both B and T LCM-primed lymphocytes.

Animals↗

PubMed1975

Persistent LCM virus infection in the mouse. Immunity and tolerance.

The initiation of persistent infections with the Traub strain of the LCM virus is dependent not only on the number of immunocompetent cells present in the infected animals but probably also on the fact that the virus depresses the development of the bone marrow cells and causes a pronounced immunosuppression at the T cell level. By analysing the events leading to the termination of the virus carrier state by adoptive immunization, it was clearly demonstrated that the cellular immunity provoked was solely responsible for the virus elimination. Furthermore, helper T cells were shown to be necessary for the production of antibodies, which also occurs in adoptively immunized mice. In view of this finding, further experiments were performed, which strongly indicated that neither LCM-primed B cells nor LCM-primed helper T cells are present in mice that are persistent virus carriers. Similarly, neither cellular immunity to the LCM virus nor the presence of enhancing factors or suppressor cells could be detected. It is concluded that C(3)H mice that are persistent virus carriers have developed a humoral as well as a cellular immunological tolerance to the LCM virus.

Animals↗

PubMed1974

Twp populations of T lymphocytes immune to the lymphocytic choriomeningitis virus.

In this report seven different parameters were employed to investigate the spleen and lymph node cells from mice at the early and the late state of immunity to the lymphocytic choriomeningitis (LCM) virus. Distinct differences were observed. Morphological studies revealed a different size distribution of the cells in the preparations from the early and the late state of immunity. The cell mixtures of early immune cells contained many more large and blast-like lymphoid cells than the other. Where the cell function was concerned, the cytotoxic activity against LCM virus-infected target cells was almost entirely a function of the early immune cells, and our data strongly indicate that enhancement does not play any role for the disappearance by time of this cell activity. The antiviral effect after transfer to acutely infected animals was also predominantly a function of the early immune cells and the same was the case concerning the ability to protect against a lethal acute infection. However, the early immune cells were almost inactive after transfer to chronically infected virus carriers, whereas transplants of late immune cells to such mice had a very strong antiviral effect. The resistance to X irradiation also varied. Even high X-ray doses could not destroy the function of early immune cells, whereas the function of the late immune cells was readily impaired by X-ray treatment. The early and the late immune cells have one thing in common-both are susceptible to treatment with anti-theta serum. Because of the differences observed between the early and the late immune cells, it is concluded that they belong to different cell populations. However, because of the common susceptibility to anti-theta serum, probably both populations are T-cell lymphocytes. The implications of the results and the role of the different cells in the combat of the viral infection are discussed.

Animals↗

PubMed1974

Defects in the immune system of mice infected with lymphocytic choriomeningitis virus.

Acute lymphocytic choriomeningitis virus infection of adult mice is associated with general immunosuppression, which develops during the 2nd week of the infection and persists for a period of 2 to 3 months. Studies of some cellular events in the immune system of infected mice brought to light a number of findings which seemed relevant to this immunosuppressive effect. Colony-forming stem cells, which may act as the precursors of the lymphoid cells, were temporarily inhibited during the first period of the infection. Presumably this inhibition also affected the thymus cells, which decreased dramatically at the same time. At a later stage of infection, defects developed within the population of immunocompetent cells, and this was most probably a consequence of the preceding suppression of the precursor cells. The defects in the immunocompetent cells were temporally related to the immunosuppression and seemed to be the ultimate cause of this phenomenon. At all events, antibody-forming cells were not damaged by the virus. In studies of neonatally infected baby mice, it was found that the development of immunological responsiveness was completely abolished for the first 2 weeks of life. It is therefore probable that the generation of immunocompetent cells was also affected in the babies. Evidence was obtained supporting the hypothesis that this effect played an important role for the induction of tolerance to the virus in the neonatally infected mice.

Animals↗

PubMed1972