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Requirement of MyD88 for macrophage-mediated islet xenograft rejection after adoptive transfer.
- Source :
-
Transplantation [Transplantation] 2007 Mar 15; Vol. 83 (5), pp. 615-23. - Publication Year :
- 2007
-
Abstract
- Background: Porcine antigen primed and CD4+ T-cell activated macrophages are able to migrate to and destroy porcine xenografts. However, the specific signaling mechanisms involved remain to be identified.<br />Methods: In this study macrophages which lack the universal toll-like receptor (TLR) adaptor MyD88 were used to investigate the role of TLR in the recognition and activation of macrophages in islet xenograft rejection. Macrophages were isolated from rejecting MyD88(-/-) and wild-type C57BL/6 mice that were recipients of neonatal porcine pancreatic cell cluster (NPCC) xenografts, and were transferred to NPCC recipient NOD-SCID mice.<br />Results: Both wild-type C57BL/6 and MyD88(-/-) mice rejected NPCC xenografts 8 and 10 days, respectively after transplantation, and the grafts were heavily infiltrated with CD4+ T cells and macrophages. However, graft infiltrating macrophages from rejecting MyD88(-/-) recipients demonstrated impaired up-regulation of TLR expression and impaired activation phenotype, when compared to those from rejecting C57BL/6 recipients. Transfer of NOD-SCID recipients with macrophages from rejecting C57BL/6 mice resulted in NPCC xenograft rejection along with massively infiltrated macrophages 8 days after transfer, whereas NPCC xenografts in NOD-SCID mice transferred with macrophages from rejecting MyD88(-/-) mice remained intact until the end of this study, 90 days after transfer, with insulin-positive islets and no infiltration by macrophages.<br />Conclusion: This study demonstrates that deletion of MyD88 causes impaired macrophage activation after pig islet xenotransplantation. However, graft survival is not prolonged and xenografts are rejected rapidly by alternate mechanisms.
- Subjects :
- Animals
Female
Flow Cytometry
Gene Expression Regulation
Islets of Langerhans Transplantation immunology
Islets of Langerhans Transplantation pathology
Macrophage Activation
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88 deficiency
Myeloid Differentiation Factor 88 genetics
Polymerase Chain Reaction
Swine
Toll-Like Receptors physiology
Adoptive Transfer
Graft Rejection immunology
Islets of Langerhans Transplantation physiology
Macrophages immunology
Myeloid Differentiation Factor 88 physiology
Transplantation, Heterologous pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0041-1337
- Volume :
- 83
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 17353783
- Full Text :
- https://doi.org/10.1097/01.tp.0000253759.87886.39