Submitted May 5, 2008
Accepted December 13, 2008
Improved outcome of allogeneic bone marrow transplantation due to breast-feeding-induced tolerance to maternal antigens
Kazutoshi Aoyama, Motoko Koyama, Ken-ichi Matsuoka, Daigo Hashimoto, Tatsuo Ichinohe, Mine Harada, Koichi Akashi, Mitsune Tanimoto, and Takanori Teshima*
Biopathological Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan
Center for Cellular and Molecular Medicine, Kyushu University Graduate School of Medical Science, Fukuoka, Japan
Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
* Corresponding author; email: tteshima{at}cancer.med.kyushu-u.ac.jp.
Exposure of offspring to noninherited maternal antigens (NIMAs) during pregnancy may have an impact on transplants 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 breast-feeding after birth, we tested whether breast milk could mediate the tolerogenic NIMA effect. We found that oral exposure to NIMAs by breast-feeding 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 breast-feeding on the outcome of transplantation.
