Restoration of allograft responsiveness in B rats by interleukin 2 and/or adherent cells

Abstract

LEW X BN)F1 cardiac allografts survive 1 wk in unmodified LEW recipients (MST +/- SD = 8.3 +/- 1.2 days) but indefinitely (greater than 100 days) in B rats, produced by 750 R sublethal x-radiation 3 to 4 wk after adult thymectomy and reconstitution with syngeneic bone marrow cells from thymectomized thoracic duct-drained donors. Graft survival appears independent of blocking antibodies and is not mediated by suppressor cells or loss of graft immunogenicity. The unresponsive state is eventually reversed by adoptive transfer of 10(8) spleen cells from nonimmune (MST +/- SD = 27.5 +/- 4.7 days) or alloimmune (MST +/- SD = 21.5 +/- 1.9 days) syngeneic animals. In contrast, concomitant administration of 2 X 10(7) thioglycollate-stimulated peritoneal exudate adherent cells plus 10(8) alloimmune syngeneic spleen cells produced acute allograft rejection in 50% of B recipients within 10 to 12 days, while in every instance grafts underwent acute rejection (MST +/- SD = 10.0 +/- 1.4 days) in B recipients treated with interleukin 2 (IL 2) rich conditioned supernatant plus sensitized cells. In vitro studies revealed that adherent cells from B rats possessed less than 50% the capacity of adherent cells from normal animals either to support the Con A-stimulated uptake of 3H-thymidine by splenic T cells or to promote production of IL 2 by spleen cells depleted of adherent cells. Altered lymphocyte migration patterns in B recipients may also contribute to prolonged allograft survival secondary to adherent cell dysfunction.