title: Naturally acquired tolerance and sensitization to minor histocompatibility antigens in healthy family members.
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 CD8(pos) minor histocompatibility (H) antigen-specific cytotoxic T lymphocytes (T(CTL)) and CD8(pos) minor H antigen-specific T regulator cells (T(REG)) in peripheral blood cells obtained from 17 minor H antigen-disparate mother-offspring pairs. Absence of minor H antigen-specific T(REG), as marked by the feasibility to expand T(CTL) from isolated tetramer(pos) populations, was observed in 6 mothers and 1 son. The presence of minor H alloantigen-specific T(REG) was observed in 4 mothers and 5 sons. These T(REG) were detected within isolated tetramer(dim) staining fractions and functioned in a CTLA-4-dependent fashion. Our study indicates that both T(CTL) and T(REG) 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.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. a.g.s.van_Halteren@lumc.nl
authors.forename: Astrid G S
authors.initials: AG
authors.lastname: van Halteren
authors.forename: Ewa
authors.initials: E
authors.lastname: Jankowska-Gan
authors.forename: Antoinette
authors.initials: A
authors.lastname: Joosten
authors.forename: Els
authors.initials: E
authors.lastname: Blokland
authors.forename: Jos
authors.initials: J
authors.lastname: Pool
authors.forename: Anneke
authors.initials: A
authors.lastname: Brand
authors.forename: William J
authors.initials: WJ
authors.lastname: Burlingham
authors.forename: Els
authors.initials: E
authors.lastname: Goulmy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D006182:H-Y Antigen / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology; D008875:Middle Aged; D011247:Pregnancy / Q000276:immunology*; D033581:Stem Cell Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006182:H-Y Antigen