title: Effect of graft-versus-host disease on anti-tumor immunity.
abstract: BCL1, a spontaneous B cell leukemia of BALB/c origin, is rejected by C.B-20 (Ighb, H-40b) but not BALB/c (Igha, H-40a) mice. Adoptive transfer of C.B-20 anti-BCL1 effector cells specific for the minor histocompatibility Ag H-40a protects irradiated C.B-20 but not BALB/c recipients. Because C.B-20 donor cells could potentially generate graft-vs-host disease (GVHD) in BALB/c recipients, we investigated the possibility that GVHD prevents the anti-tumor effect. GVHD was induced in (C.B-20 X B10.D2)F1 [H-2d, H-40b X H-2d,H-40b] recipients after injection of B10.D2-primed C.B-20 donor cells. GVHD was indicated by the histologic appearance of tissue sections from C.B-20----F1 livers, target organs of GVHD, which showed a marked mononuclear cell infiltrate around the portal tracts and central veins. In addition, splenic lymphocytes from these mice had altered CD4/CD8 ratios and were unable to respond to the polyclonal activators Con A and LPS. The mitogen unresponsiveness was at least partially due to the presence of a suppressor cell, because proliferation of normal spleen cells to Con A and LPS was suppressed upon addition of C.B-20----F1 spleen cells. Further immune dysfunction was evident by the inability of T cells from mice with GVHD to generate a CTL response to H-2 alloantigens. Addition of C.B-20----F1 spleen cells to F1 responder cells at the induction of culture did not prevent generation of CTL, indicating that a suppressor cell was not responsible for the lack of CTL activity. In this setting of GVHD, F1 recipients were able to reject BCL1 upon adoptive transfer of C.B-20 anti-BCL1 effector cells. These data indicate that GVHD-induced immune dysfunction does not inhibit the activity of antileukemia T cells.
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235-9048.
authors.forename: K L
authors.initials: KL
authors.lastname: Schreiber
authors.forename: J
authors.initials: J
authors.lastname: Forman
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D016827:CD8 Antigens; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D006183:H-2 Antigens / Q000276:immunology; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007116:Immunization, Passive; D015448:Leukemia, B-Cell / Q000276:immunology* / Q000628:therapy; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D006183:H-2 Antigens