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Biomedical subjects

R Kiessling

Publications and source records attributed to R Kiessling.

At least 163 records · Page 9Linked to original sources
PubMed1977

Generation of natural killer cells: an autonomous function of the bone marrow.

Generation of natural killer (NK) cells in spleens from radiation chimeras produced between pairs of histocompatible 'high' and 'low' NK-reactive mouse strains has been investigated. Spleen cells of high-reactive recipients reconstituted with bone marrow from low-reactive mice were found to be low reactive. Conversely, spleen cells of low mice grafted with bone marrow or fetal liver cells from high donors were high reactive. Similarly, the age-related changes of NK activity were shown to be expressed at the bone marrow precursor cell level. These results indicate that the generation of natural killer cells is an inborn and autonomous function of the bone marrow and does not depend on the genotype or other influences of the host environment.

Animals↗
PubMed1977

Genetic variation in antibody response and natural killer cell activity against a Moloney virus-induced lymphoma (YAC).

Antibody formation against the Moloney virus-determined surface antigen (MCSA) was found to be under genetic control. In the (A X C57BL)F1 cross one dominant gene played a major role, resulting in bimodal distribution of the antibody response. This gene showed no linkage to H-2, IgG heavy chain immunoglobulin allotype, the coat color markers B and C, and five different isozyme markers representing chromosome numbers 1, 4, 7, 8 and 9. Antibody response to MCSA was not correlated with antibody titers against the virion proteins, confirming that MCSA was an independent entity. There was no relationship between the segregation of natural killer cell activity and antibody response in a [(A X C57BL) X A] backcross population.

Animals↗
PubMed1976

Killer cells: a functional comparison between natural, immune T-cell and antibody-dependent in vitro systems.

Previous reports have shown that spleen cells from nonimmune adult mice of certain strains do regularly kill Moloney leukemia virus-induced lymphomas in short-term 51Cr release assays. This naturally occuring killer (NK) cell had low adherent properties and had the morphological appearance of a lymphocyte. Still it lacked surface characteristics of mature T or B lymphocytes. In the present report a functional study was carried out, comparing in parallel the NK system, the T-cell killing across an H-2 barrier (anti-P815), and the antibody-dependent cell-mediated chicken red blood cell (CRBC) system. In contrast to the effector cells in the CRBC system, the NK cells were insensitive to erythrocyte antibody complement (EAC) rosette depletion and would pass through nylon wool columns. NK activity was not inhibited by the presence of heat-aggregated human or mouse gamma globulin, in contrast to the strong inhibition noted in the CRBC system. Sensitivity to trypsin pretreatment was noted in the NK system as well as in the immune P815 system, whereas the CRBC system was relatively trypsin resistant. Antitheta plus complement eliminated the anti-P815 activity, but did not touch the NK activity. The present results thus further distinguish the NK cell from cytotoxic T lymphocytes or from antibody-dependent killer cells.

Animals↗
PubMed1976

Non-T-cell resistance against a mouse Moloney lymphoma.

We have previously shown that spleen cells from normal mice contain lymphocytes that kill certain in vitro-grown Moloney lymphoma lines in a 51Cr release test. The killing activity shows a marked dependence on the genotype of the donor mouse. In vivo rejection studies with a Moloney lymphoma line in various normal semisyngeneic F1 hybrids showed a clear positive correlation between in vitro natural cytotoxicity and in vivo rejection. Thus mice can be grouped as high- or low-reactive according to their in vitro cytolytic behavior as well as their in vivo rejection potential. A lymphoid cell without detectable T- or B-cell markers is responsible for the in vitro killing effect. The present study also shows that the in vivo growth inhibitory function is T-cell-independent. Lymphoid cells depleted of T- and B-cells and transferred together with Moloney lymphoma cells into an irradiated syngeneic recipent were highly efficient in delaying tumor growth. Furthermore, syngeneic or semisyngeneic thymecto-mized, irradiated, fetal-liver-reconstituted mice showed if anything an increased in vivo resistance to a Moloney lymphoma compared to control mice. In contrast, tumor cells histoincompatible with regard to the H-2 locus showed the expected preferential growth in the thymectomized animals. We thus conclude that the major in vivo resistance against transplantation of the syngeneic or semisyngeneic Moloney lymphoma used in this study is T-independent.

Animals↗
PubMed1975

Genetic variation of in vitro cytolytic activity and in vivo rejection potential of non-immunized semi-syngeneic mice against a mouse lymphoma line.

Spleens of normal young mice of certain genotypes contain lymphocytes that can kill strain A-derived YAC-1 and some other in vitro-grown Moloney lymphoma lines in a 51Cr-release cytotoxic test. We have previously shown that mouse strains can be classified as high or low reactors in this test. F(1) hybrids between low- and high-reactive strains are high-reactive. In the present study, strain-A mice and eight different A F(1) hybrids were tested in parallel for their spleen-cell-mediated killing effect in vitro and their ability to reject graded numbers of YAC ascites or in vitro cultivated cells in vivo. There was a clear correlation between in vitro cytotoxicity and in vivo rejection in all tested genotypes. In segregating (A times C57Bl) times A backcross mice, in vivo rejection of YAC cells was H-2 linked. This is in line with the earlier backcross analysis of the in vitro cytotoxicity, suggesting a polygenic control with at least one H-2 linked factor.

Animals↗
PubMed1975

"Natural" killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype.

In the spleens of young, adult mice there exist naturally occurring killer lymphocytes with specificity for mouse Moloney leukemia cells. The lytic activity was directed against syngeneic or allogeneic Moloney leukemia cells to a similar extent, but was primarily expressed when tested against in vitro grown leukemia cells. Two leukemias of non-Moloney origin were resistant and so was the mastocytoma line P815. Although killer activity varied between different strains of mice, the specificity of lysis was the same as indicated by competition experiments using unlabeled Moloney or other tumor cells as inhibitors in the cytotoxic assays. Capacity to compete and sensitivy to lysis by the killer cells were found to be highly positively correlated. Analysis of the kinetics of the cytotoxic assay revealed a rapid induction of lysis within one to four hours, arguing against any conventional in vitro induction of immune response. No evidence was found of soluble factors playing any role in the cytolytic assay.

Animals↗
PubMed1975

"Natural" killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell.

Normal mice contain cytolytic cells with specificity for in vitro grown mouse Moloney leukemia cells. Such killer cells are most frequent in the spleens; lymph node and bone marrow contain less and thymus virtually no killer activity. Peak activity is found around one to three months of age. Spleen cells from genetically athymic mice are as active killer cells as those from normal mice of the same strain. Treatment with anti-theta serum plus complement followed by removal of adherent and surface Ig positive cells by filtration through anti-Ig columns will leave between 1-5% of the original spleen cell population from a normal mouse. These cells have the morphology of small lymphocytes and perhaps contain all of the total original killer activity of the spleen against the Moloney leukemia cells. Such killer enriched cells are devoid of T and B lymphocytes and largely fail to function in antibody induced, cell-mediated lysis against antibody-coated chicken erythrocytes. It is concluded that the spontaneous selective cytotoxic activity of normal mouse spleen cells against Moloney leukemia cells is exerted by small lymphocytes of yet undefined nature.

Age Factors↗
PubMed1975

Comparison of the allospecific and viral-specific immune responses to irradiated versus formaldehyde-fixed allogeneic Moloney lymphoma cells in CBA mice.

Two groups of adult CBA mice were immunized with 10-7 allogeneic Moloney lymphoma (YAC) cells. These YAC (H-2a) cells, which were either irradiated with 6000 R (Group i) or were formaldehyde fixed (Group II), were injected i.p. at weekly intervals for 3 weeks. Four days following the last injection, sera and lymphocytes were collected and tested in vitro for activity against either allospecific antigens (H-2d target cells) or viral-specific antigens, namely, Moloney leukemia virus (MLV). Both groups of animals developed measurable cellular and humoral immunity to the virally determined antigens. However, only the animals in Group i, immunized with irradiated cells, developed detectable immunity to H-2d. Immune and control lymphocytes were tested in microcytotoxicity tests and by 51Cr release. Antibody was assessed by complement-dependent cytotoxicity, indirect membrane immunofluorescence, virus neutralization, and antibody-dependent lymphocyte cytotoxicity. Group I serum, which had both anti-MLV and anti-H-2 antibodies, was absorbed with either living or formaldehyde-fixed YAC cells. The living cells were able to remove both H-2 and MLV antibodies. On the other hand, the formaldehyde-fixed cells removed no H-2 antibody but were able to remove MLV antibody, although less efficiently than living cells. These data indicate that formaldehyde fixation selectively impaired the H-2 antigens, leaving the viral antigenicity relatively intact. Differences between the immune responses to MLV-determined antigens and to H-2 antigens were demonstrated in many of the parallel in vitro tests.

Animals↗
PubMedDate not supplied

The value of a direct agglutination test in the diagnosis of cutaneous and visceral leishmaniasis in Ethiopia.

The usefulness and sensitivity of a direct agglutination test (DAT) in the diagnosis of cutaneous leishmaniasis due to Leishmania aethiopica infection has been investigated. Formalin-fixed, trypsin-treated and Coomassie blue-stained Leishmania promastigotes of various origins were used as antigens. L. major, L. donovani, L. aethiopica but not L. tropica antigen preparations were able to distinguish sera from individuals infected with Leishmania from sera of uninfected controls, although the titres of sera from patients with localized cutaneous leishmaniasis were low. Comparable results were obtained when the same sera were tested using freshly prepared antigen or antigen stored for 10 months at 4 degrees C. The assay was also used to monitor improvement of disease status following treatment of diffuse cutaneous leishmaniasis patients, and it was found to correlate well with the changing clinical status of the patients.

Adolescent↗
PubMedDate not supplied

Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy.

Metazoan organisms may discriminate between self and non-self not only by the presence of foreign antigens but also by the absence of normal self markers. Mammalian adaptive immune responses use the first strategy, with the additional requirement that foreign antigens are recognized in the context of self-major histocompatibility complex (MHC) products at the cell surface. Aberrant cells which fail to express MHC products adequately can therefore avoid detection. A more primitive but complementary defence system, eliminating such cells on the basis of absent self-markers, is suggested by a re-interpretation of phenomena associated with metastasis and natural resistance. We now show that murine lymphoma cells selected for loss of H-2 expression are less malignant after low-dose inoculation in syngeneic hosts than are wild-type cells, and that the rejection of such cells is non-adaptive. On the basis of our data, we suggest that natural killer cells are effector cells in a defence system geared to detect the deleted or reduced expression of self-MHC.

Animals↗
PubMedDate not supplied

Inhibition of mouse bone marrow granulocyte-macrophage colony formation by factors derived from natural killer cells: an in vitro model for hybrid resistance.

Investigations were performed to study whether soluble factors produced by NK-cells could mediate "hybrid resistance" in vitro. NK-cells enriched from spleens of B6D2F1 hybrid mice were incubated with parental B6 bone marrow, and the effect of the derived supernatants on the development of granulocyte-macrophage colony forming cells (GM-CFC) was assessed. Cell free supernatants obtained from low density cells (LDC) of B6D2F1 hybrids stimulated with bone marrow cells (BMC) from B6 mice inhibited GM-CFC formation. The inhibition was similar using B6, D2 or B6D2F1 bone marrow cells as the targets for GM-CFC growth. Our findings suggest that NK cells from F1 hybrid mice when stimulated with BMC from B6 mice release inhibitory factors, different from IFN-gamma and that this production may represent a mechanism of natural resistance to parental H-2b bone marrow grafts.

Animals↗