TOKITA Daisuke    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Induction of endotoxin tolerance inhibits alloimmune responses.
Journal	Formal name：Transplant immunology Abbreviation：Transpl Immunol ISSN code：09663274/09663274
Domestic / Foregin	Foregin
Volume, Issue, Page	16(3-4),pp.158-65
Author and coauthor	Ishiyama Kohei, Ohdan Hideki, Tokita Daisuke, Shishida Masayuki, Tanaka Yuka, Irei Toshimitsu, Asahara Toshimasa
Publication date	2006/11
Summary	It was recently reported that the induction of endotoxin tolerance (ET), which is defined as a reduced response to a lipopolysaccharide (LPS) challenge following the first LPS encounter, inhibits major histocompatibility complex (MHC)-restricted antigen presentation. This raises the question whether alloimmune responses can be inhibited by inducing ET in transplant donors. C57BL/6 mice were treated with a low dose of LPS prior to a challenge with a high dose of LPS to induce ET. Hearts from endotoxin-tolerized C57BL/6 mice were transplanted to BALB/c mice. The survival of the endotoxin-tolerized heart allografts was significantly prolonged. By using irradiated splenocytes from C57BL/6 mice and allogeneic splenocytes from BALB/c mice, a mixed lymphocyte reaction (MLR) assay was performed. The MLR assay used CFSE, and revealed that the splenocytes from the endotoxin-tolerized mice failed to induce the proliferation of allogeneic CD4(+) and CD8(+) T cells. Cytokine analyses of the supernatant of the MLR culture using endotoxin-tolerized stimulators revealed a distinct shift in the Th 1/Th 2 balance toward the Th 2-type response. The induction of ET increased the proportion of myeloid-related dendritic cells (DCs) expressing molecules necessary for antigen presentation, which favor the development of a Th 2 response; however, it reduced the proportion of lymphoid-related DCs expressing those molecules, which favor the development of the Th 1 response. Although the relevance of these findings with regard to the prolonged survival of the endotoxin-tolerized heart allografts remains to be elucidated, this is the first study to demonstrate that the induction of ET in donor animals inhibits alloimmune responses.
DOI	10.1016/j.trim.2006.06.002
PMID	17138048