The effect of T lymphocyte depletion on neonatal tolerance induction, graft-vs.-host disease and cellular chimerism.
Treatment with a monoclonal anti-Thy-1 antibody and complement completely prevented C57BL spleen cells from causing graft-vs.-host disease following their inoculation into newborn CBA mice. The proportion of mice that became tolerant to C57BL antigens, as measured by skin grafting, was significantly less compared with mice given (CBA X C57BL)F1 hybrid cells. This was not due to the elimination of T cells, for antibody-treated F1 cells induced tolerance as readily as complement-treated control F1 cells. To investigate whether the apparent superiority of F1 cells over C57BL cells is attributable to differences in the mechanism inducing and maintaining unresponsiveness, two approaches were followed. First, the level of donor cell chimerism in the spleens of tolerant animals was studied. Though no difference between F1 and C57BL cells was uncovered, the presence of T cells in the donor inocula favored the establishment of chimerism. Second, the involvement of suppressor T cells was examined in adoptive transfer experiments. Splenic suppressor T cells were associated with tolerance regardless of how it was elicited. Preliminary results with F1 cells show that the tolerogenic property is not confined to any one cell type. It is proposed that the greater tolerogenicity of F1 cells is brought about by the presence of host-type (self) antigens, which enable the tolerogenic signals to operate without recourse to antigen processing by host cells.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion; D002678:Chimera; D003165:Complement System Proteins / Q000276:immunology; D006086:Graft vs Host Disease; D007108:Immune Tolerance; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016038:Skin Transplantation; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D003165:Complement System Proteins