Die in utero und orale Exposition zu “Non-inherited Maternal Antigens (NIMA)” bewirkt eine natürliche Transplantationstoleranz in Mäusen

Abstract

To study the phenomenon of tolerance to non-inherited maternal antigens (NIMA), we used two F1 backcross breeding schemes: C57BL/6 (H-2^b/b) males were mated either with B6D2F1 (H-2^b/d) or B6C3F1 (H-2^b/k) females, whereby 50% of the offspring were H-2^b/b mice exposed to NIMA^d or NIMA^k -alloantigens. Controls were H-2^b/b offspring of H-2^b/b mothers, either inbred C57BL/6 mice, or F1 backcross mice from matings with heterozygous fathers. We found that 53% of the H-2^b/b offspring from NIMA^d-breedings accepted fully allogeneic DBA/2 (H-2^d/d) heart grafts indefinitely whereas all controls rejected their grafts within 11 d. Consistent with these in vivo results we found that the frequency of γ-IFN-producing T cells responding to allogeneic and semiallogeneic APC expressing NIMA^d was 60 – 80% lower in exposed vs. non-exposed control mice. In the H-2^b/b offspring from NIMA^k-breedings the survival of fully allogeneic C3H heart grafts was not prolonged. Analysis of IFN-γ producing T cells to H-2^k stimulator cells revealed a reduction of only 30 – 34%. To investigate the effect of in utero vs. oral exposure to maternal antigens, NIMA^d and regular B6 offspring were exchanged for each other directly after birth. When transplanted with DBA/2 grafts we did not see a beneficial effect of either exposure alone.