Naturally acquired tolerance and sensitization to minor histocompatibility antigens in healthy family members

Abstract

Abstract Bidirectional cell transfer during pregnancy frequently leads to postpartum persistence of allogeneic cells and alloimmune responses in both the mother and in her offspring. The life-long consequences of naturally acquired alloimmune reactivity are probably of importance for the outcome of allogeneic stem cell transplantation. We investigated the presence of CD8pos minor histocompatibility (H) antigen–specific cytotoxic T lymphocytes (TCTL) and CD8pos minor H antigen–specific T regulator cells (TREG) in peripheral blood cells obtained from 17 minor H antigen–disparate mother-offspring pairs. Absence of minor H antigen–specific TREG, as marked by the feasibility to expand TCTL from isolated tetramerpos populations, was observed in 6 mothers and 1 son. The presence of minor H alloantigen–specific TREG was observed in 4 mothers and 5 sons. These TREG were detected within isolated tetramerdim staining fractions and functioned in a CTLA-4–dependent fashion. Our study indicates that both TCTL and TREG mediated alloimmunity against minor H antigens may be present in healthy female and male hematopoietic stem cell donors, potentially influencing graft-versus-host reactivity in different ways.