PubMed Health⌕ Search

Biomedical subjects

L Olsson

Publications and source records attributed to L Olsson.

At least 145 records · Page 8Linked to original sources

Autoreactive natural killer-like cells from agar-cloned murine bone marrow cells.

Natural surveillance against malignant cells has been ascribed to so-called natural killer (NK) cells. These cells attack tumour cells without prior antigen stimulation and may also be cytotoxic to non-malignant cells. NK cells are routinely demonstrated by their cytotoxic activity against various types of tumour cell in vitro, but elucidation of the characteristics of the cytotoxic cells has hitherto been hampered by the lack of techniques by which NK cells can be isolated. Here we demonstrate murine NK-like activity from bone marrow cells cloned in semi-solid agar medium for granulocyte-macrophage colony formation. Data obtained indicate that such procedures considerably improve the possibility of obtaining quite pure NK cell populations by which the NK cell phenomenon may be studied in more detail.

Animals↗

Autoreactive cells as mediators of the natural defense against malignant tumors.

The present paper suggests that the natural defense mechanisms against tumors are part and a logical consequence of the natural mechanisms that maintain tissue uniformity. We further suggest that biologic errors steadily are accumulated in cells with increasing age, and that the number of cells with insufficient functional capacity (aberrant cells) increases with age. Since this increasing number of aberrant cells threatens the uniformity and function of the cell population, aberrant cells must be removed in order to maintain tissue uniformity. The aberrant cells may be removed by autonomous destruction or by cytotoxic attack by autoreactive cells. Such autoreactive cells are present in the normal organism throughout life, may be suppressed by thymus-derived cells, and may be activated by immune adjuvants. We suggest from theoretic and experimental reasons that the major function of autoreactive cells is the maintenance of tissue uniformity and tissue homeostasis within a cell population.

Animals↗

Human-human hybridomas producing monoclonal antibodies of predefined antigenic specificity.

We report the establishment of human-human hybridomas producing monoclonal antibody of predefined antigenic specificity. The U-266 human myeloma cell line was incubated in the presence of 8-azaguanine, and a rapidly growing, 8-azaguanine-resistant, hypoxanthine/amethopterin/thymidine (HAT) medium-sensitive mutant line, U-266AR1, was selected. These cells were fused with lymphoid cells from uninvolved spleens removed at staging laparotomy from patients with untreated Hodgkin's disease who had been previously sensitized to the chemical allergen 2,4-dinitrochlorobenzne. Hybrid cell cultures growing in HAT medium were screened for IgG production. Positive cultures were selected and their supernatants were tested in a solid-phase radioimmunoassay for reactivity with dinitrophenyl hapten coupled to bovine serum albumin. Cultures producing specific antibody were subcloned and expanded, and their antibody products were shown to be monoclonal by biosynthetic labeling and sodium dodecyl sulfate/polyacrylamide gel electrophoresis.

Antibodies↗

Natural polyclonality of spontaneous AKR leukemia and its consequences for so-called specific immunotherapy.

Young female AKR mice made leukemic by iv inoculation of 10(3) spontaneous AKR thymoma cells were treated with repeated injections of irradiated cells from the same tumor. Treatment began 1 day after injection of the viable cells. The cytotoxicity of sera and lymphoid cells from healthy mice immunized with lymphoma cells from either treated or nontreated mice with leukemia grafts revealed that the tumor cells could be subdivided into four distinct antigenic types. One type (clone A) accounted for about 97% of the lymphoma cells in each mouse with spontaneous leukemia, whereas the remaining 3% were subdivided into three other distinct antigenic types (clones B, C, and D). Lymphoma cells from treated mice with grafted leukemia were never clone A type but either clone B, C, or D type. Repeated sc injections of 10(7) irradiated cells from spontaneous AKR thymomas induced from 15 to 34% cure in mice with grafts of leukemia cells. Treatment with only clone A induced about 32% cure, whereas treatment with clone B, C, or D had no beneficial effect. Treatment with 10(7) cells each of clone A plus clone B gave 33% cure; clone A plus clone B plus clone C, 45%; and all four clones cured 92% of the mice with leukemia grafts. The efficiency of immunotherapy may be influenced by the natural clonality of the tumor to be treated.

Animals↗

Immunoadjuvant treatment of primary grafted and spontaneous AKR-leukemia. I. Treatment efficiency correlated to autoimmune reactivity.

Young AKR mice grafted i.v. with 10(1) or 10(3) cells from spontaneous AKR thymomas were treated with repeated i.v. injections of BCG or subcutaneous injections of irradiated AKR thymoma cells. BCG often cured mice from graft leukemia, whereas the effect of irradiated thymoma cells was less effective. Mice that did not develop graft-leukemia after graft of 10(1) leukemia cells and BCG treatment showed a spontaneous leukemia in 30% of the cases later. Ninety percent of nongrafted mice developed spontaneous leukemia whether BCG-treated or not. General immune reactivity as assessed in individual mice by T and B lymphocyte mitogen tests as well as the hemolytic plaque-forming cell assay had no clear correlation to the effects of immune adjuvants in respect to survival. In contrast, occurrence of self-directed immune reactions were clearly correlated to survival and cure of grafted and BCG-treated mice as revealed by assays both in vitro and in vivo. However, 13 to 25% of the mice apparently cured of leukemia developed a wasting-like syndrome that sometimes terminated in death. The immplications of self-directed immune reactions as mediators of the anti-neoplastic effects of immunoadjuvants.

Adjuvants, Immunologic↗

Immune reactions with cytotoxic activity to "self" in natural surveillance of aberrant cells.

Cytotoxic autoreactive lymphoid cells have been demonstrated to be a normal immunologic component in both normal and tumor-bearing organisms. The cells have a high antineoplastic potential. They are cytotoxic in vitro to non-immunogenic tumor cells, and a high in vivo activity of such cells may be positively correlated to in vivo regression of tumors. It is suggested that the cytotoxic activity of cytotoxic autoreactive cells reflects a natural mechanism to removal of all types of aberrant cells of which malignant cells are only a subset. It is further deduced that such mechanisms must be independent of cell surface neoantigens, and that cytotoxic autoreactive mechanisms with high probability therefore also are efficient against spontaneous malignant tumors.

Animals↗

Specificity of the inhibition of DNA synthesis by extracts from cloned normal, sarcoma-virus-transformed and revertant 3T3 cells.

Extracts containing tissue-specific DNA-inhibitory activity were prepared from normal FL (Swiss) and BALBc3T3 cells, from these cells transformed with sarcoma virus and from revertants cloned from the transformed cell lines. By testing all extracts on all cell lines we found that (1) production of and susceptibility to the inhibitors were decreased in transformed BALB/c cells (2) specificity varied with expression of the transforming genome, as an extract from a given cell line inhibited the growth of its cell of origin, e.g. revertant, more than normal or transformed cells, and (3) there was also a DNA-synthesis stimulator.

Animals↗