Mechanisms of allografted tumor rejection: the roles of T cells in allograft rejection mediated by a type of bone marrow-derived macrophage.
Allografted tumor rejection does not occur in the absence of T cells, but the main effector cells responsible for the rejection are allograft-induced macrophages (AIM). We examined the roles of T cells in the AIM-mediated rejection of Meth A (H-2d) tumor cells from C57BL/6 (H-2b) mice. Irradiation of C57BL/6 mice abrogated both the induction of AIM and the allograft rejection. Reconstitution of the irradiated mice with F1 (C57BL/6 X C3H/He: H-2b/k) bone marrow cells led to the appearance of H-2b/k haplotype of AIM exclusively in the rejection site and to allograft rejection, indicating that radiosensitive cells prerequisite for both the induction of AIM and allograft rejection were bone marrow-derived cells, and that the progenitors of AIM existed in the bone marrow cells to be activated into AIM in the rejection site. To understand the role of T cells in the induction of AIM, we used adult-thymectomized, X-irradiated C57BL/6 mice reconstituted with F1 bone marrow (ATXBM). The ATXBM mice could neither induce AIM nor reject allogeneic Meth A cells, whereas adoptive transfer of F1 lymph node T cells to the ATXBM mice restored not only the induction of AIM but also rejection of the allograft. Among the lymph node T cells, CD4-, but not CD8+, cells were found to be essential for the activation of AIM progenitors to AIM; and CD8+ T cells were further required for rejection, at least in part, to enhance the number of AIM in the rejection site.
Ushio-Umeda
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Y
Department of Cell Biology, Osaka Bioscience Institute, Suita, Japan.
Yoshida
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R
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005354:Fibrosarcoma / Q000139:chemically induced / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008748:Methylcholanthrene; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D010529:Peritoneal Cavity; D051381:Rats; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D008748:Methylcholanthrene