Graft-versus-host disease after brown Norway-to-Lewis and Lewis-to-Brown Norway rat intestinal transplantation under FK506

Abstract

In LEW rats treated daily with variable doses of FK506 for 14 days and weekly thereafter, successful intestinal transplantation from fully allogeneic BN donors never was complicated by fatal GVHD. In contrast, with LEW-to-BN transplantation, rejection was difficult to control and GVHD developed after the end of the daily treatment. However, FK506 in high daily doses continued after the initial 14-day course could prevent this GVHD or even reverse it after allowing its onset. Further experiments did not clarify why the BN rat was an "easy" donor and "difficult" recipient. In unaltered animals the lymphocyte population of normal LEW rats had a higher proportion of T cells, fewer B cells, and a lower CD4:CD8 ratio than normal BN rats. However, one-way MLR reactions of the BN and LEW combinations were generally similar in either direction and not affected differently by the addition of FK506 to the medium. The two-way lymphocyte traffic from graft to host lymphoid organs and vice versa also was similar with BN-to-LEW and LEW-to-BN models. The BN rat may be a useful tool to investigate inadequately explained mechanisms of GVHD.

Figure 1

Inhibition of one-way MLR (using mesenteric lymphocytes) with different concentrations of FK506. LEW responder–BN stimulator (open circle); BN responder–LEW stimulator (closed circle).

Figure 2

Body weight changes after LEW-to-BN transplantation with different dose schedules. FK506 was given for 14 days after transplantation in groups 6–9. In group 9, subsequent weekly injections were given of FK506 (1 mg/kg: arrow).

Figure 3

Body weight change of BN recipients of LEW intestine (group 10) after GVHD was diagnosed, whose original FK506 treatment was 0.64 mg/kg for 14 days. When GVHD developed with a 15% loss of weight, FK506 treatment was resumed with 1.28 mg/kg/day for 7 days, then 0.64 mg/kg/day thereafter.

Figure 4

Donor and recipient phenotypes of graft mesenteric lymph node lymphocytes at different times after LEW-to-BN and BN-to-LEW transplantation under FK506 treatment (0.64 mg/kg/day for 14 days).

Figure 5

Percentage of donor cells in recipient peripheral blood, spleen, and mesenteric lymph nodes after BN-to-LEW and LEW-to-BN intestinal transplantation.