Natural killing and antibody-dependent cellular cytotoxicity of tumor targets are mediated by the same effector cell.
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Biomedical subjects
Publications and source records attributed to M S Hamilton.
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Evidence is presented that in rats the subcutaneous site can extend privilege to both major histocompatibility complex (MHC)-incompatible (FI X DA)F1 leads to FI and MHC-compatible LEW leads to FI skin allografts, approximately doubling the median survival time of similar grafts transplanted orthotopically. Unlike graft dosage, "gene" dosage was an important variable in that grafts from (FI X DA)F1 donors significantly outlived those from DA strain donors. Prior splenectomy of the hosts did not prejudice the capacity of their subcutaneous sites to extend privilege. It was found that the hemagglutinin response incited by subcutaneous grafts was significantly delayed compared with that evoked by similar grafts transplanted orthotopically or intraperitoneally. This observation, coupled with our inability to demonstrate the passage of India ink to regional lymph nodes after its injection into the dermis of established subcutaneous grafts of syngenic skin, is consistent with the concept that poor endowment of the subcutaneous milieu with both blood and lymph vessels is the principal factor underlying its hospitality to allografts.
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The immune responses of pregnant mice to alloantigens were studied using the 51chromiun release assay. Four populations of lymphoid effector cells were studied. Control lymphoid cells were from normal, virgin BALB/c females, and BALB/c females specifically immunized to (BALB/c X C3H) F1 spleen cells. Experimental lymphoid cells were from BALB/c females pregnant by BALB/c males (syngeneically pregnant) or C3H males (allogeneically pregnant). Target cells were 51chromiumlabeled phytohemagglutinin-induced lymphoblasts from BALB/c and (BALB/c X C3H) F1 animals. Pooled lymph node and spleen cells from BALB/c females pregnant by C3H males were not cytotoxic for (BALB/c X C3H) F1 target cells. Lymphoid cells were transferred to sublethally irradiated syngeneic recipients that were simultaneously challenged with (BALB/c X C3H) F1 alloantigens. One week later, the spleen cells of the recipient animals were used as effector lymphoid cells. Lymphoid cells from normal, syngeneically pregnant, and allogeneically pregnant animals were equally cytotoxic for (BALB/c X C3H) F, target cells. Lymphoid cells from BALB/c animals specifically immunized to (BALB/c X C3H) F, alloantigens were highly cytotoxic for these target cells. Compared with the unmixed cell populations, mixtures of lymphoid cells from norman and syngeneically or allogeneically pregnant animals were hyporesponsive to alloantigenic challenge. Serum from neither syngeneically pregnant nor allogeneically pregnant animals inhibited the response of normal lymphoid cells to alloantigen. Immunoregulation in pregnancy was discussed.
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Monoclonal antibody MA21 recognized a 44kDa plasma membrane protein on F9 teratocarcinoma cells, trophectoderm of mouse peri-implantation-stage blastocyst and ectoplacental cone cells of 5 day postcoitum implanted blastocyst (Vernon, Linnemeyer and Hamilton, 1989). We show here that this antigen is expressed by trophoblast cells of the maturing placenta. Immunohistochemical assays of early and mature placental tissue sections, indirect immunofluorescence labelling of placental cultures and blastocyst outgrowths in vitro, and immunoprecipitation of 35S-labelled NP-40 extracts of placental cultures indicate the presence of a plasma membrane-associated antigen with the same characteristics as MA21 antigen of peri-implantation embryos and F9 teratocarcinoma cells. In sections of placentae, antigen-positive cells are always situated in a thin layer between trophoblastic giant cells and maternal tissue. In cultures of postimplantation stage embryos, attached trophoblast cells express MA21 antigen initially, but following transformation to the giant cell state, antigen is no longer expressed. These results indicate the presence of a plasma membrane protein antigen associated with a distinct population of cells believed to be trophoblast. We believe that these cells are the foremost trophoblast cells opposing maternal decidua and that they may give rise to secondary trophoblastic giant cells.
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