Antilymphocytic antibodies and bone marrow transplantation. XI. Evidence that reduced Thy-1 expression in Thy-1.1 mice prevents suppression of graft-versus-host disease with anti-Thy-1 monoclonal antibodies.
Considerable variations in the suppression of graft-versus-host disease with monoclonal anti-Thy-1 antibodies were found to relate to substantial differences noted in the expression of mouse Thy-1 marker on lymph node and spleen cells of Thy-1.1 (AKR/J, C57BL/6.Thy-1.1) and Thy 1.2 (AKR/Cu, C57BL/6) mice. Thy-1.1 mice showed a population of 22% (AKR/J) or 13% (C57BL/6-Thy-1.1) of Thy-1 negative cells among peripheral T cells carrying Ly-1 marker. This was in sharp contrast with Thy-1.2 mice, where as expected practically all peripheral T cells expressed both Thy-1 and Ly-1. Double-marker analysis on FACScan revealed that the Thy-1-/Ly-1+ cell population identified in Thy-1.1 but not in Thy-1.2 mice doubtless represents T cells because they express CD3 and either the L3T4 (CD4) or Lyt2 (CD8) phenotype. Using quantitative fluorescence-measurement techniques, it was found in addition that the Thy-1 antigen-binding sites on Thy-1+ cells from Thy-1.1 mice are considerably fewer than those present in Thy-1.2 mice. In fact, the Thy-1 antigen-binding sites approximate the level of Ly-1 density. Consequences of the reduced expression of Thy-1 became apparent in vivo: (1) lymphnode and splenic T cell areas in Thy-1.1 mice were clearly less depleted when Thy-1.1 and Thy-1.2 mice had been injected with rat IgG2b anti-Thy-1 mAb; and (2) GvHD was prevented completely in fully mismatched mice by anti-Thy-1 mAb if the donor mice expressed Thy-1.2 but was barely delayed if the donors expressed Thy-1.1. Thus the present study provides a transplantation model for comparing differences in T antigen density and their consequences for antibody-induced immunosuppression.
Mysliwietz
J
J
GSF, Institut für Immunologie, Munich, Federal Republic of Germany.
Thierfelder
S
S
Hoffmann-Fezer
G
G
Kummer
U
U
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000950:Antigens, Ly / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006086:Graft vs Host Disease / Q000276:immunology*; D007124:Immunoenzyme Techniques; D007165:Immunosuppression Therapy; D007518:Isoantibodies / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D000954:Antigens, Surface; D007518:Isoantibodies; D018800:Thy-1 Antigens; C035678:anti-Thy antibody