Maternal Modification of Antigenicity: An Immunologic Mechanism to Ensure Survival of Mammalian Fetuses

Summary

It was postulated that maternal modification of antigenicity was the immunologic mechanism that prevents the rejection of the hybrid fetus as an allograft. Growth and function of hybrid tissue were tested in a parental strain of AKR mice. These mice were preimmunized by rejection of CBA, (CBA × AKR)F₁, and (AKR × CBA)F₁ skin allografts, exposed to lethal total-body X irradiation, and inoculated with the 3 types of allogeneic marrow. Variations in survival patterns determined whether the bone marrow graft was established and could function in presensitized recipients. Pre-immunization against CBA tissue prevented the establishment of a CBA marrow graft but only interfered with the function of hybrid marrow grafts. Preimmunization with hybrid skin prevented normal function of CBA marrow and, to a lesser extent, the (CBA × AKR)F₁ marrow; it did not, however, impede the growth and function of (AKR × CBA)F₁ marrow. Surviving chimeras were tolerant to skin allografts containing CBA tissue antigens, even though they had previously rejected similar skin allografts. Normal growth and function of normal adult marrow from (♀AKR × ♂CBA)F₁ donors in AKR recipients, preimmunized against paternal antigens by contact with hybrid tissue, were analogous with a maternal-fetal relationship, but without mechanical barriers or undeveloped antigenicity characteristic of fetal tissue. These experiments demonstrated that this immunologie mechanism alone could ensure survival of (♀AKR × ♂CBA)F₁ tissue. However, other supplementary mechanisms may also exist to provide additional survival advantage in the fetus.