Analysis of donor reactive cells in ALS-treated mice bearing skin allografts after the intrathymic injection of donor specific spleen cells.
The intrathymic injection of donor spleen cells into antilymphocyte serum (ALS)-treated mice induces significant prolongation of donor skin grafts. The intrathymic route of antigen presentation in this model is superior to the intravenous route in achieving unresponsiveness. To elucidate possible mechanisms involved in the induction of unresponsiveness in ALS-treated mice after intrathymic injection of donor spleen cells, we have analysed the reactivity of lymphoid cells from unresponsive mice in various ways. Deletion of donor reactive cells has been studied using the Mls antigen system. Functional inactivation was analysed by a sequential study of the frequency of donor reactive cells. Suppressor cell activity was studied using an adoptive transfer assay. Deletion of donor reactive cells was partial and occurred largely in the spleen in both early and late stages of unresponsiveness. The frequency of donor reactive cytotoxic cells was suppressed in both spleen and lymph nodes from day +/- 13 until grafts were rejected, with the exception of a rebound period at day +/- 22. In contrast, donor reactive cells were not deleted or inactivated in the thymus. Suppressor cell activity could only be detected in mice bearing long-term grafts. These results suggest that donor reactive cytotoxic cells are functionally inactivated in the spleen and nodes in the early and late stages of unresponsiveness after intrathymic injection of antigen. In contrast, donor reactive cells in the thymus do not appear to be affected.
Ohzato
H
H
Department of Surgery, New England Deaconess Hospital, Boston, MA 02215, USA.
Wood
M L
ML
Gottschalk
R
R
Monaco
A P
AP
D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D006085:Graft Survival; D016219:Immunotherapy, Adoptive; D007267:Injections; D008198:Lymph Nodes / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D016038:Skin Transplantation; D013045:Species Specificity; D013154:Spleen / Q000276:immunology* / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D000961:Antilymphocyte Serum