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MD1 Expression Regulates Development of Regulatory T Cells
Abstract
Intense interest has centered around the role of a subset of regulatory T cells, CD4+CD25+ Treg, in controlling the development of auotimmune disorders, allograft rejection, infection, malignancy, and allergy. We previously reported that MD1, a molecule known to be important in regulation of expression of RP105, also was important in regulating alloimmunity, and that blockade of expression of MD1 diminished graft rejection in vivo. One mechanism by which an MD1-RP105 complex exerts an effect on immune responses is through interference with an LPS-derived signal delivered through the CD14-MD-2-TLR4 complex. We show below that LPS signaling for Treg induction occurs at higher LPS thresholds that for effector T cell responses. In addition, blockade of MD1 functional activity in dendritic cells (using anti-MD1 mAbs, MD1 antisense deoxyoligonucleotides, or responder cells from mice with deletion of the MD1 gene), resulted in elevated Treg induction in response to allogeneic stimulation (in vivo or in vitro) in the presence of LPS. These data offer one mechanistic explanation for the augmented immunosuppression described following anti-MD1 treatment.
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CD180/Ly86 affect the immune response to lipopolysaccharide (LPS) by interfering with an LPS-derived signal delivered through the CD14-MD2-TLR4 complex.
“Together CD180/Ly86 affect the immune response to lipopolysaccharide (LPS) by interfereing with an LPS-derived signal delivered through the CD14-MD2-TLR4 complex.35”
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Murine Liver Antigen Presenting Cells Control Suppressor Activity of CD4+CD25+ Regulatory T Cells *
Wiegard, C., Frenzel, C., Herkel, J., Kallen, K.-J., Schmitt, E., & Lohse, A. W. (2005) · Hepatology · doi:10.1002/hep.20756 · Cited by 97
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Weekes, M. P., Antrobus, R., Talbot, S., Hör, S., Simecek, N., Smith, D. L., Bloor, S., Randow, F., & Lehner, P. J. (2012) · Journal of Proteome Research · doi:10.1021/pr201135e · Cited by 82
Metadata
- Authors
- Gorczynski, R. M., Kai, Y., & Miyake, K.
- Affiliations
- Departments of Surgery and Immunology, University Health Network and the Toronto Hospital , Toronto, Ontario ,
- Department of Microbiology and Immunology, Division of Infectious Genetics, Institute of Medical Science, University of Tokyo , Tokyo ,
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-07
- Volume
- 177
- Issue
- 2
- Pages
- 1078-1084
- ISSN
- 0022-1767
- 1550-6606
- Cited by
- 17
- References
- 1
- Language
- en
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