Role of lymphokine-activated killer cells as mediators of veto and natural suppression.
Fresh bone marrow cells have veto activity but little if any NK activity. By contrast, lymphokine-activated bone marrow cells have potent natural suppressor as well as veto activity, and also have cytolytic activity characteristic of lymphokine-activated killer cells. Veto activity of fresh bone marrow cells is eliminated by 9 Gy irradiation and by depletion of cells expressing Qa-2, but is unaffected by removal of cells expressing Thy-1, Qa-5, Ly-5, or asialo GM1. By contrast, the veto and NS activities of lymphokine-activated bone marrow cells are both abrogated by C lysis depletion of cells expressing Qa-2, Qa-5, Thy-1, asialo GM1, NK1, and Ly-11, but are unaffected by depletion of cells expressing Ly-2. Bone marrow cells depleted of Qa2+ cells fail to generate veto or natural suppressor activity when cultured in Con A-conditioned medium, unlike bone marrow cells depleted of mature NK1.1+ NK cells. Cloned NK cell line F8 is able to mediate both natural suppression and veto. These findings indicate that bone marrow veto and natural suppression are not mediated by T or NK cells present de novo in the bone marrow, but are dependent on proliferating cells that phenotypically resemble pre-NK cells. The progeny of these cells have the phenotype and functional activity of lymphokine-activated killer cells, and are capable of directly mediating both veto and natural suppression.
Azuma
E
E
Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan 48201.
Kaplan
J
J
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D003602:Cytotoxicity, Immunologic; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology*; D008213:Lymphocyte Activation; D008222:Lymphokines; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010641:Phenotype
D000954:Antigens, Surface; D008222:Lymphokines