Role of Natural Killer Cells on Engraftment of Human Lymphoid Cells and on Metastasis of Human T-Lymphoblastoid Leukemia Cells in C57BL/6J-scidMice and in … (original) (raw)

tastasis of human lymphomas and suggest that innate immune factors in addition to NK cell function mediate The severe combined immunodeficiency (scid) mutaresistance to engraftment of normal human peripheral tion was backcrossed onto the C57BL/6J strain backblood leukocytes. ᭧ 1996 Academic Press, Inc. ground in order to study the role of natural killer (NK) cells in rejection of normal and malignant human lymphohematopoietic cells. C57BL/6J-scid/scid mice showed INTRODUCTION severe loss of mature T and B cells accompanied by increased percentages of NK1.1 / cells and myeloid cells. C.B-17 mice homozygous for the severe combined im-Although little or no serum immunoglobulin was detectmunodeficiency (scid) mutation have been widely utiable prior to 2 months of age, all mice tested had circulating immunoglobulin by 7.5 months of age. C57BL/6J-scid/ lized as hosts for both normal and malignant human scid mice had markedly elevated levels of both hemolytic lymphoid cells (1-6). Although C.B-17-scid/scid mice complement activity and NK cell activity compared with lack adaptive immune function (2, 7), they possess a C57BL/6J-/// controls. Weekly injections with antirobust innate immune system (8). We have hypothe-NK1.1 antibody resulted in elimination of NK cell activsized that human peripheral blood mononuclear cells ity in C57BL/6J-scid/scid mice throughout 8 weeks of (PBMC) 3 or human hematopoietic stem cell entreatment. Although human CEM-C7 T lymphoblastoid graftment appears to be limited by host natural killer tumor cells grew slowly in unmanipulated C57BL/6J-(NK) cell activity and by other factors associated with scid/scid mice, anti-NK1.1 treatment resulted in ininnate immunity (8, 9). In vivo suppression with polycreased growth accompanied by metastasis of human clonal rabbit antibody to asialo-GM-1 has been used lymphoma cells to the brain, liver, and kidney. In conwidely to reduce levels of NK cell activity in C.B-17trast to T lymphoblastoid tumor cells, nonmalignant huscid/scid mice prior to engraftment with human man peripheral blood mononuclear cells engrafted at lymphoid cells or tissues (1, 10, 11). However, expreslow levels in anti-NK1.1-treated as well as in unmanipusion of this glycolipid is not confined to NK cells. Asialolated C57BL/6-scid/scid mice. Backcrossing of the beige GM-1 is present on at least some activated T cells (12), (bg J) mutation onto the C57BL/6-scid/scid genetic stock thymic epithelial cells (13), Thy-1 / dendritic epidermal caused decreased NK cell activity accompanied by grancells (13, 14), and macrophages (15). Thus, in vivo ulocyte defects. C57BL/6-scid/scid bg J /bg J mice showed treatment with this polyclonal antibody may deplete metastasis of human CEM-C7 cells to the brain and other multiple cell populations. organs but supported only low levels of engraftment In order to facilitate the selective elimination of NK with human peripheral blood mononuclear cells. These cell activity, the scid mutation was backcrossed onto results demonstrate that NK cells, in the absence of an the C57BL/6J inbred background. In contrast to C.Badaptive immune system, function in resistance to me