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Treatment of an Established Graft-versus-Host Reaction in AKR Mice by Adoptive Immunotherapy¹

Division of Clinical Hematology, Department of Medicine [S. J. C., M. M. A.], and Department of Pathology [A. R. E.], Rhode Island Hospital, Providence, Rhode Island 02902

A model system in AKR mice for the induction and cure of a clinically evident graft-versus-host disease is reported. Graft-versus-host disease is initiated by i.p. injections of cyclophosphamide (250 mg/kg body weight) into female AKR mice, on Day 0. This is followed by i.v. injections of 45 x 10⁶ normal spleen cells (NSC) from male C57BL/6J mice. Median survival time for these mice is 33.4 ± 4.5 days.

Following the administration of C57BL/6J NSC, AKR mice were rescued from graft-versus-host disease by the following treatment protocol: (a) Day 6, 35 x 10⁶ DBA/2 NSC given i.v.; (b) Day 10, cyclophosphamide i.p. (150 mg/kg body weight); (c) Days 11 and 16, 35 x 10⁶ AKR NSC given i.v.

These experiments demonstrate that graft-versus-host reaction can be eliminated by coupling a graft-versus-host reaction with a graft-versus-graft reaction and restoring the host by immunocompetent syngeneic cells.

¹ First article of a series. This research was supported in part by the George V. Meehan Fund-Clinical Research in Blood Diseases, The Phyllis Kimball Johnstone and H. Earle Kimball Foundation, and the Louis and Goldie Chester Memorial Fund.

Received 7/ 2/74. Accepted 11/18/74.