Pregnancy induces minor histocompatibility antigen-specific cytotoxic T cells: implications for stem cell transplantation and immunotherapy.
Recipients of HLA-identical stem cell transplants have a poorer transplant outcome if the donor is female rather than male. We analyzed whether pregnancy primes for minor histocompatibility (H) antigens. Peripheral blood mononuclear cells (PBMCs) from healthy multiparous female blood donors were depleted for CD4+, CD14+, CD16+, and CD19+ cells, stained with minor H antigen-specific HLA-A2 tetramers, sorted by fluorescence-activated cell sorting, and tested for cytotoxic activity. Minor H antigens HY-, HA-1-, and HA-2-specific cytotoxic T cells (CD8+, CD45RA-) were present in PBMCs from 4 of 7 female donors up to 22 years after the last delivery. Interestingly, in 2 of the 4 cases microchimerism of the putative immunizing minor H antigen was observed. Thus, pregnancy can lead to alloimmune responses against the infant's paternal minor H antigens. The minor H antigen immunization status of female donors raises important questions for the clinical practice of stem cell transplantation.
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Rob M
RM
Verdijk
Antoinette
A
Kloosterman
Jos
J
Pool
Maarten
M
van de Keur
Albert M I H
AM
Naipal
Astrid G S
AG
van Halteren
Anneke
A
Brand
Tuna
T
Mutis
Els
E
Goulmy
D000911:Antibodies, Monoclonal / Q000097:blood; D018941:Antigens, CD19 / Q000096:biosynthesis; D001782:Blood Donors; D015704:CD4 Antigens / Q000096:biosynthesis; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000096:biosynthesis; D006648:Histocompatibility; D015395:Histocompatibility Antigens Class I / Q000737:chemistry; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D011247:Pregnancy; D017452:Receptors, IgG / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000379:methods*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D015704:CD4 Antigens; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D018950:Lipopolysaccharide Receptors; D015778:Minor Histocompatibility Antigens; D010455:Peptides; D017452:Receptors, IgG