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Biomedical subjects

S Thierfelder

Publications and source records attributed to S Thierfelder.

At least 127 records · Page 7Linked to original sources
PubMed1980

Influence of the recipient thymus on the maturation of T-lymphocytes in H-2 different radiation chimeras.

Graft-versus-host reactions in mice can be suppressed by incubation of the donor cells with T-cell-specific antibodies prior to transplanting them into lethally irradiated recipients. Since reconstitution of the immune functions in these recipients requires the formation of a new T-lymphocyte population, we investigated whether H-2 differences between recipient thymus and donor stem cells as well as an age dependent thymic involution impaired the maturation of immunocompetent T-lymphocytes. For this purpose the immune response of different chimeric mice against SRBC and third party skin grafts as well as the repopulation of the lymphatic organs with T-lymphocytes was evaluated. Chimeras of the type CBL leads to CBL/CBA and CBL/CBA leads to CBA were used for the experiments. In addition chimeras which had been thymectomized, transplanted with the thymus of one parent strain, lethally irradiated and transfused with bone marrow from other parent strain were analyzed. In all chimeric combinations, even in the case of complete H-2 difference between donor cells and recipient thymus, a normal or almost normal reconstitution of the immune response against SRBC and incompatible skin grafts were detected. Furthermore age-involuted thymi returned to normal morphologically and functionally after bone marrow transplantation. The repopulation of the lymphatic organs in the investigated chimeric mice was remarkably similar to normal controls. This indicates that hemopoietic stem cells and/or lymphopoietic progenitors may differentiate in a thymus in spite of H-2 differences to functional T-lymphocytes able to respond against SRBC and incompatible skin grafts.

Animals↗
PubMed1980

Bone marrow transplantation into recipients sensitized against donor-type T cells.

Immunization of prospective bone marrow recipients with thymocytes of the marrow donor strain prevented subsequent hemopoietic engraftment of the marrow. Immunization with thymocytes of a third party strain sharing the marrow donor's theta alloantigen but not his histocompatibility antigens permitted chimaerism and suppressed GVH in mice. Bone marrow of rat strains of the Th-1.1 group did not take in mice sensitized against mouse Th-1.1 thymocytes. This observation lead to the conclusion that hemopoietic stem cells of rats but not of mice express an early thymic and even prethymic antigen. This antigen is not restricted to the Th-1.1 specificity: rabbit anti-rat thymocyte globulin absorbed in a way which removed stem cell toxicity from a rabbit anti-mouse thymocyte globulin prevented hemopoietic engraftment when incubated with rat bone marrow before transfer to irradiated mice. Serologically this antiserum reacted with thymocytes as well as lymphocytes in the rat bone marrow but less with lymph node cells. An antiserum against rat lymph node cells was rendered T cell specific by absorption. It defined a postthymic T antigen lacking on stem cells, bone marrow lymphocytes and thymus. It labeled lymphocytes in the interfollicular T dependent area of lymph nodes by an immunohistochemical method. T cells in rats were thus found to express a prethymic and/or a postthymic antigen. Implications of theta alloantigens for the suppression of GVH in polytransfused bone marrow grafted patients are discussed.

Animals↗
PubMed1980

Fc-receptor-bearing cells in spleen of mice injected with cell-free Ehrlich ascites fluid (EAF).

The kinetics of different cell populations (T and B) and subpopulations (one bearing easily releasable FcR and one bearing stable FcR) was followed in spleens of mice after one single i.p. injection of EAF. The number of FcR bearing cells doubled within 2-7 days after EAF injection. This increase was due to cells bearing temperature sensitive FcR and was accompanied by the doubling of theta positive cells. These results, supported by the demonstration of doubly labeled (theta+FcR+) cells, suggest that EAF injected into normal mice causes the appearance of T-cells expressing easily releasable FcR. These cells, according to Fridman et al. (1977) are suppressor cells. Maximal increase of theta positive cells and of cells with temperature sensitive FcR detected in vitro coincided with the maximum of the suppressive activity of EAF detected in vivo.

Animals↗
PubMed1980

Antibody incubation of human marrow graft for prevention graft versus host disease.

An in vitro incubation of incompatible donor bone marrow by xenogenic anti-T-cell globulin (ATG) suppressed an otherwise lethal GvH reaction in animal models. An application of this principle to clinical bone marrow transplantation was successfully tried in three patients with acute lymphoblastic leukemia. Preparation of the specific anti-human T-cell globulin (ATCG-H) was carried out by absorption of anti-human thymocyte globulin with liver-kidney homogenate, chronic lymphocytic leukemia cells of B-cell type, and erythrocytes. Subsequent testing revealed that the serum still reacted with human T-cells but no longer reduced the number of colony-forming units in culture (CFU-C). All three bone marrow recipients were treated by chemotherapeutic conditioning and total body irradiation followed by grafting of in vitro treated bone marrow from HLA-identical siblings. The transplantation of the bone marrow was well tolerated and no major side effects were encountered. No patient so far (24, 7, 6 months) has shown any signs of GvHD. The in vitro pretransplantation treatment of bone marrow with anti T-globulin may be a new approach to the prevention for GvHD in man.

Adolescent↗
PubMed1980

Specific anti-marmoset T-cell globulin: cytotoxic and mitogenic properties.

A virus-transformed marmoset lymphoblastoid cell line (LCL) with T-cell characteristics was used for the production of rabbit anti-marmoset T-cell globulin (RAMTG). Exhaustive absorption of the crude antiserum with kidney-liver homogenate and pooled marmoset B-LCL yielded a T-cell-specific antibody. Specificity of the absorbed RAMTG was evidenced by plateau formation in the cytotoxic activity on marmoset peripheral blood lymphocytes (PBL) and clear discrimination between marmoset T-LCL and B-LCL. Unexpectedly, the absorbed RAMTG was not cytotoxic for human PBL. Assays for mitogenic activity showed that unabsorbed RAMTG exhibited mitogenic activity on marmoset, but not on human or baboon PBL. Unabsorbed rabbit anti-human T-cell globulin (RAHTG) induced cellular proliferation in human and baboon PBL, whereas marmoset or Saimiri sciureus PBL showed no response. Absorbed RAMTG did not stimulate DNA synthesis of marmoset PBL. In conclusion, the specific RAMTG may be useful for studies on the functional role of T-lymphocytes in the marmoset immune response to organ allografts or infectious agents.

Animals↗
PubMed1980

Immunoglobulin expression on theta-positive leukemic cells in AKR/J mice.

The expression of surface immunoglobulin was studied on cells of theta-positive AKR leukemia during repeated weekly passages of ascitic cells. It could be shown that the percentage of Ig-positive cells varied considerably (0-25%) and that this was accompanied by variations in the expression of theta-antigen on the cell surface. This was interpreted as repression and derepression of genes coding for surface antigen possibly at the translational level.

Animals↗
PubMed1980

Rhesus incompatibility and aplastic anemia as the consequence of split chimerism after bone-marrow transplantation for severe combined immunodeficiency.

A patient with severe combined immunodeficiency received three transplants of bone marrow from the HLA-B- and -D-identical mother. The first transplantation led to a severe graft-versus-host reaction followed by immunological reconstitution. A split chimerism was found with engraftment only of the maternal lymphocytes. Five months after the transplantation an autoimmune hemolytic anemia was observed which was due to rhesus incompatibility as well as polyspecific antibodies. At the same time agranulocytosis developed and 9 mth after the first transplantation the child suffered from aplastic anemia. Two further attempts failed to engraft the maternal hematopoiesis. The child died during the treatment with cyclophosphamide as conditioning for a third transplantation.

Agranulocytosis↗
PubMed1980

Fractionated total body irradiation and autologous bone marrow transplantation in dogs: hemopoietic recovery after various marrow cell doses.

Hemopoietic recovery was studied in dogs given 2400 R fractionated total body irradiation within one week and graded doses of cryopreserved autologous bone marrow. Complete hemopoietic recovery including histology was observed after this dose and sufficient doses of marrow cells. Doses of more than 5.5 X 10(7) mononuclear marrow cells/kg body weight were sufficient for complete recovery in all dogs, 1.5 to 5.5 X 10(7) cells/kg were effective in some of the dogs and less than 1.5 X 10(7) cells/kg were insufficient for complete recovery. Similarly, more than 30,000 CFUc/kg body weight were required for hemopoietic recovery. The optimal marrow cells dose which has been defined as the minimal dose required for the earliest possible recovery of leukocyte and platelet counts was 7-8 X 10(7) mononuclear marrow cells/kg body weight. It has been concluded that fractionated total body irradiation with 2400 R does not require greater doses of marrow cells for hemopoietic reconstitution than lower single doses and that the hemopoietic microenvironment is not persistently disturbed after this dose.

Animals↗