The use of parabiosis for investigating the mechanism of transplantation tolerance in bone marrow chimeras induced by total lymphoid irradiation.

The mechanism of transplantation tolerance in total lymphoid irradiation (TLI)-induced semiallogeneic bone marrow chimeras without clinical evidence of graft-versus-host disease (GVHD) was investigated using the technique of surgical parabiosis. When held in parabiosis with normal BALB/c mice, BALB/c---- (BALB/c x C57BL/6)F1 (BALB----F1) chimeras survived 7-9 days, significantly (P less than 0.001) shorter than the 12-19 day survival of normal F1 hybrids kept in parabiosis with normal BALB, and in contrast to indefinite (greater than 200 days) survival of syngeneic BALB parabiotic partners. When C57 skin grafts were placed on BALB mice held in parabiosis with BALB----F1 chimeras, C57 skin grafts survived 50-60 days, in contrast to 10-14 days in normal BALB recipients (P less than 0.001). Lethal GVHD, induced in sublethally irradiated F1 recipients by 10(7) BALB spleen cells, could not be delayed or prevented by cotransfer of 10(7) to 30 x 10(7) tolerant BALB spleen cells obtained from stable BALB----F1 chimeras. GVHD reactivity of BALB spleen cells isolated from BALB----F1 chimeras tolerant of C57 could not be recovered by depletion of Lyt2 cytotoxic suppressor cells. Taken together, in the absence of suppressive capacity by suppressor cells, these data support functional clonal deletion as the primary mechanism responsible for the maintenance of unresponsiveness to host alloantigens in TLI-induced semiallogeneic chimeras, since no protection against induction of GVHD could be documented in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)