Improved outcome of allogeneic bone marrow transplantation due to breastfeeding-induced tolerance to maternal antigens.
Exposure of offspring to noninherited maternal antigens (NIMAs) during pregnancy may have an impact on transplantations performed later in life. Using a mouse model, we recently showed that bone marrow transplantation (BMT) from NIMA-exposed offspring to the mother led to a reduction of graft-versus-host disease (GVHD). Since offspring can also be exposed to NIMAs by breastfeeding after birth, we tested whether breast milk could mediate the tolerogenic NIMA effect. We found that oral exposure to NIMAs by breastfeeding alone was sufficient to reduce GVHD, and that in utero exposure to NIMAs is required for maximum reduction of GVHD. The tolerogenic milk effects disappeared when donor mice were injected with CD25 monoclonal antibodies during the lactation period, suggesting a CD4(+)CD25(+) regulatory T cell-dependent mechanism. Our results suggest a previously unknown impact of breastfeeding on the outcome of transplantation.
Aoyama
Kazutoshi
K
Biopathological Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Koyama
Motoko
M
Matsuoka
Ken-ichi
K
Hashimoto
Daigo
D
Ichinohe
Tatsuo
T
Harada
Mine
M
Akashi
Koichi
K
Tanimoto
Mitsune
M
Teshima
Takanori
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000941:Antigens / Q000494:pharmacology*; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy*; D007108:Immune Tolerance / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007774:Lactation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008892:Milk / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D000941:Antigens; D015704:CD4 Antigens; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit