Hearts of newborn mice were cut into small pieces, the fragments transplanted under the ear skin of adult recipients, and the graft survival followed visually (pulsating fragments were considered viable). Donor-recipient combinations were chosen from H-2 congenic (recombinant and mutant) strains in such a way as to provide differences in the entire H-2 complex or in only a small portion of it. The data obtained indicate that a difference between the donor and the recipient in either K, D, or I regions suffices for the rejection of the heart fragments. The rejection is often accompanied by the production of antibodies against classical H-2 antigens (in the case of K- or D-region disparities) or Ia antigens (in the case of I region disparities). In some instances, the antibodies persist in the recipient for more than 50 days. We conclude from these experiments that the same loci that cause acute skin graft rejection (H-2K, H-2D, and H-2I) are responsible for heart graft rejection. Furthermore, we also conclude that serologically Ia-negative tissues may carry Ia antigens in sufficient quantities to stimulate the production of Ia antibodies.

Animals↗

PubMed1976

Serum-blocking factors versus specific cellular tolerance in long-term survival of rat heart allografts.

Long-term survival of Ag-B compatible rat heart allografts was obtained by short-term treatment of the recipients with antilymphocytic serum (ALS). Graft survival apparently was based on a specific change in the hosts rather than on persistent nonspecific effects of ALS. The hosts were not fully tolerant in that they were able to reject secondary skin allografts from the heart donor strain, although in a delayed fashion. The long-surviving heart allografts retained their immunogenicity as they were rejected when retransplanted to new hosts. The passive transfer of serum from long-term heart graft acceptors to new hosts receiving fresh allografts delayed rejection by several days. This effect was seen only with the serum from long-term acceptors suggesting that serum-blocking factors were involved in long-term survival of the heart allografts. However, the ability of adoptively transferred lymphoid cells to break tolerance to a heart allograft residing in a classically tolerant host was tested. In contrast to normal lymphoid cells, cells from the long-term acceptors were unable to break tolerance, suggesting that a specific cellular tolerance had been induced in this cell population. Moreover, a serum from the long-term acceptors failed to block the breakage of tolerance by normal lymphoid cells.

Animals↗