The graft-versus-host reaction and immune function. II. Recruitment of pre-T-cells in vivo by graft-versus-host-induced dysplastic thymuses following irradiation and bone marrow treatment.
The graft-versus-host (GVH) reaction induces thymic dysplasia and an arrest in T cell differentiation. Studies were performed to test the effect of irradiation and reconstitution with bone marrow on GVH-induced thymic dysplasia and T cell differentiation. GVH reactions were induced in CBAxAF1 adult mice by the injection of A strain lymphoid cells. All GVH-reactive mice were immunosuppressed by day 7 after GVH induction and thymic dysplasia was evident by day 24. Forty days after the induction of the GVH reaction the mice were irradiated (850 rads) and repopulated with 10-15 X 10(6) syngeneic or parental bone marrow cells. Thirty days after irradiation and bone marrow reconstitution, GVH-reactive mice were used for histological and functional studies. These mice displayed near-normal thymus morphology with scattered epithelial cells in the medulla, and normal numbers of Thy-1-positive cells. Donor cells had totally repopulated thymuses of irradiated bone marrow reconstituted mice by day 19 after irradiation. T helper cell function did not recover in the reconstituted mice. These results suggest that (1) the process responsible for GVH-induced thymic dysplasia is radiosensitive, and (2) the thymus has the potential to regenerate a normal structure, but fails to regain normal function.
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D006087:Graft vs Host Reaction / Q000528:radiation effects; D051379:Mice; D008805:Mice, Inbred A; D008806:Mice, Inbred AKR; D008808:Mice, Inbred CBA; D011828:Radiation Chimera; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018800:Thy-1 Antigens; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology*
D000954:Antigens, Surface; D018800:Thy-1 Antigens