Age-related factors in cyclosporine-induced syngeneic graft-versus-host disease: regulatory role of marrow-derived T lymphocytes

The Effect of Combining Unfractionated Marrow from Young and Old Donors on the Incidence ofSyngeneic GVHD The next series of experiments were designed to address whether mixing unfractionated marrow from animals 1 and 6 mo of age could modify the incidence of syngeneic GVHD normally induced with bone marrow from the youngest donors alone. Bone marrow from donors 1 or >6 mo of age was transfused at first alone into lethally irradiated 8-9-wk-old recipients. As controls, two different doses, 3 x 107 and 6 x 107 nucleated cells, were used to reconstitute the recipients. The experimental groups received a total of 6 x 107 bone marrow cells derived from donors 1 and >6 mo of age mixed in equal proportion. The recipients received 30 d of CsA therapy (15 mg/kg/d), and the incidence ofsyngeneic GVHD was observed. The results are summarized in Table 1 . Recipients of bone marrow from donors 1 mo of age demon- (8) (9) wk of age) were grafted with syngeneic bone marrow derived from syngeneic rats 1 mo of age or from animals 6 mo old . The marrow was infused singly or after mixing, and the recipients were treated with a 30-d course of CsA (15 mg/kg/d). After discontinuation of CsA therapy, the animals were observed daily for the appearance of SGVHD . strated severe disease in the entire experimental group by at least day 28 after discontinuation of CsA therapy. Those that received 6 x 101 developed a more aggressive disease 3 wk earlier than those receiving 3 x 10' cells. Notably, recipients of marrow from donors >6 mo of age did not develop disease if reconstituted with 3 x 107 cells and only one of eight rats transfused with 6 x 107 cells developed mild SGVHD. Recipients of 3 x 107 cells from 1-mo-old donors combined with 3 x 107 cells from donors >6 mo of age demonstrated the same timing and incidence of clinical SGVHD as those receiving marrow from the mature donors alone. In summary, the transfusion of marrow from more mature animals influences the potential of bone marrow from immature animals to induce autoimmunity. The marrow from donors >6 mo of age contained some population(s) of cells capable of preventing the induction of syngeneic GVHD in the secondary recipient .