Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft Rejection.

Published

Journal Article

The myeloid differentiation protein 88 (MyD88) adapter protein is an important mediator of kidney allograft rejection, yet the precise role of MyD88 signaling in directing the host immune response toward the development of kidney allograft rejection remains unclear. Using a stringent mouse model of allogeneic kidney transplantation, we demonstrated that acute allograft rejection occurred equally in MyD88-sufficient (wild-type [WT]) and MyD88(-/-) recipients. However, MyD88 deficiency resulted in spontaneous diminution of graft infiltrating effector cells, including CD11b(-)Gr-1(+) cells and activated CD8 T cells, as well as subsequent restoration of near-normal renal graft function, leading to long-term kidney allograft acceptance. Compared with T cells from WT recipients, T cells from MyD88(-/-) recipients failed to mount a robust recall response upon donor antigen restimulation in mixed lymphocyte cultures ex vivo. Notably, exogenous IL-6 restored the proliferation rate of T cells, particularly CD8 T cells, from MyD88(-/-) recipients to the proliferation rate of cells from WT recipients. Furthermore, MyD88(-/-) T cells exhibited diminished expression of chemokine receptors, specifically CCR4 and CXCR3, and the impaired ability to accumulate in the kidney allografts despite an otherwise MyD88-sufficient environment. These results provide a mechanism linking the lack of intrinsic MyD88 signaling in T cells to the effective control of the rejection response that results in spontaneous resolution of acute rejection and long-term graft protection.

Full Text

Duke Authors

Cited Authors

  • Lerret, NM; Li, T; Wang, J-J; Kang, H-K; Wang, S; Wang, X; Jie, C; Kanwar, YS; Abecassis, MM; Luo, X; Zhang, Z

Published Date

  • November 2015

Published In

Volume / Issue

  • 26 / 11

Start / End Page

  • 2753 - 2764

PubMed ID

  • 25788530

Pubmed Central ID

  • 25788530

Electronic International Standard Serial Number (EISSN)

  • 1533-3450

International Standard Serial Number (ISSN)

  • 1046-6673

Digital Object Identifier (DOI)

  • 10.1681/ASN.2014080813

Language

  • eng