Two distinct populations of primary cytotoxic cells infiltrating into allografted tumor rejection sites: infiltration of macrophages cytotoxic against allografted tumor precedes that of multiple sets of cytotoxic T lymphocytes with distinct specificity to alloantigens.
It has been reported that the rejection of tumor allografts is mainly mediated by cytotoxic T lymphocytes (CTLs). Here, we characterized the cytotoxic effector cells of C57BL/6 (B6; H-2b) mice infiltrating into the rejection site of the i.p. allografted Meth A fibrosarcoma (or P815 mastocytoma) cells of H-2d origin. Two types of cytotoxic cells (i.e., CD8+ CTLs and macrophages (M phi s)) were identified by flow cytometric fractionation of the infiltrates or by specific in vitro elimination of cells either with antibody (Ab)-coated beads or with an Ab-plus complement. Of particular interest, these effector cells showed distinct and unique target specificities. First, the CTLs were inactive against transplanted tumor (e.g., Meth A) cells, whereas they were cytotoxic against donor-related concanavalin A (Con A) blasts as well as CTLL-2 (H-2b) cells transfected with a class I gene of H-2d origin. A cold target competition assay suggested that the CTLs were composed of multiple sets of T cells, each of which specifically recognized different allo-antigens. Second, the M phi s lysed the allografted tumor cells but were inert toward the Con A blasts and the CTLL-2 transfectants. Unexpectedly, the infiltration of M phi s preceded the infiltration of CTLs by several days during the course of rejection. These results indicate that two distinct populations of unique cytotoxic cells (i.e., CTLs and M phi s) are induced in the allografted tumor rejection site, and that the infiltration of cytotoxic M phi s responsible for rejection precedes that of the CTLs cytotoxic against cells expressing donor-related allo-antigens.
Yoshida
R
R
Department of Cell Biology, Osaka Bioscience Institute, Japan.
Matsuura
A
A
Einaga
K
K
Ushio
Y
Y
Yamamoto
N
N
Yoneda
Y
Y
D000818:Animals; D000906:Antibodies / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology; D003208:Concanavalin A / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation / Q000276:immunology*; D010537:Peritoneum / Q000166:cytology / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018800:Thy-1 Antigens / Q000276:immunology; D014162:Transfection
D000906:Antibodies; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018800:Thy-1 Antigens; D003208:Concanavalin A; D003165:Complement System Proteins