Antilymphocytic antibodies and marrow transplantation. V. Suppression of secondary disease by host-versus-theta-graft reaction.

An approach to block secondary disease was investigated in mice sensitized against the Th-1.1 (theta-AKR) alloantigen on the marrow donor's T cells. To avoid a concomitant sensitization against the donor's histocompatibility antigens, prospective marrow recipients were sensitized against thymocytes of a third-party strain sharing the donor's Th-1 alloantigen but not his histocompatibility antigens. Advantage was taken of the fact that rats carry a Th-1.1-like theta-antigen which induces anti-Th-1.1 antibodies in Th-1.2 mice. CBA/J and (C57BL/6 x CBA)F1 Th-1.2 mice were sensitized against rat thymocytes and tranfused with spleen and bone marrow of AKR/J Th-1.1 after irradiation with 800 to 900 R. Although unsensitized recipients died within 3 weeks of acute secondary disease, sensitized mice survived the observation period of 50 days as chimaeras. Sensitized recipients were killed by the transplantation of spleen cells from congenic AKR/Cum carrying the Th-1.2 antigen. The host-versus-theta-graft approach suppressed secondary disease following H-2-compatible and -incompatible marrow grafts. Its hemopoietic and Tcell chimaeras tolerated skin grafts of the donor strain while rejecting third-party skin grafts.