Graft-versus-host resistance induced by tolerant cell populations: evidence against clonal deletion as a mechanism of transplantation tolerance

Characterization of the effect of immunization of F1 hybrid hosts with low doses of parental cells has shown that the F1 hybrid response to the receptor for the unshared MHC antigen on the immunizing cell induces specific resistance to a GVH challenge from cells of the same parental strain. We have shown that cells from parental rats tolerant to the unshared MHC antigens are capable of inducing GVH resistance in F1 hybrids. Unlike cells from normal parental rats that induce GVH resistance only when given in low immunizing doses of 10(6) cells, 10(6)-10(8) cells from tolerant donors effectively immunize F1 hybrids. This effect does not appear to be the result of passive transfer of suppressor cells from the tolerant donor. An alternative explanation is that tolerant populations contain cells that express the receptor for the tolerated alloantigen. The finding that normal parental populations that have been deleted of receptor-bearing cells by passage through semiallogeneic intermediate hosts do not induce GVH resistance, whereas tolerant cell populations do, confirms that clonal deletion does not adequately account for the functional characteristics of the tolerant cells. Attempts to delete putative receptor-bearing cells from the tolerant population however produced equivocal results.