Clonal deletion as the mechanism of abrogation of immunological memory following liver grafting in rats.

In the rat strain combination of DA into PVG, an orthotopic liver graft has the ability to abrogate an existing state of sensitization against donor (DA) antigens. Fifty-four percent of PVG rats sensitized against DA by skin grafting accepted a DA liver graft permanently, and about half of these became systemically tolerant of DA MHC antigens, as demonstrated by permanent acceptance of a subsequent (second-set) DA skin or heart graft. The cellular basis of this tolerant state was studied in vivo. An adoptive transfer assay provided evidence for functional deletion of DA-reactive cells responsible for graft rejection from the recirculating lymphocyte pool. There was no evidence of a role for suppressor T cells in maintaining tolerance. However, a graft-versus-host assay showed normal reactivity in thoracic duct lymphocytes from tolerant animals. Hence, specific clonal deletion is apparently responsible for the abolition of immunological memory by liver grafting, but is selective in respect of the sets of alloreactive lymphocytes affected.