In:
The Journal of Immunology, The American Association of Immunologists, Vol. 196, No. 1_Supplement ( 2016-05-01), p. 140.17-140.17
Abstract:
The incidence of antibody-mediated kidney graft rejection has increased, but the key cellular and molecular participants underlying this graft injury remain unclear. We previously reported that kidney allograft rejection in CCR5−/− mice is dependent on donor-specific antibody (DSA). The current study determined if cells expressing cytotoxic function contributed to antibody-mediated kidney allograft rejection in CCR5−/− recipients. Wild type C57BL/6, B6.CCR5−/− and CD8−/−/CCR5−/− mice were transplanted with complete MHC mismatched A/J kidney grafts and intra-graft inflammatory components were followed to rejection. B6.CCR5−/− and CD8−/−/CCR5−/− recipients rejected the allografts by day 35 whereas 65% of allografts in wild type recipients survived past day 80 post-transplant. Allograft rejection in wild type recipients was associated with high titers of DSA, equivalent to those induced in CCR5-deficient recipients. Rejected allografts in C57BL/6, B6.CCR5−/− and CD8−/−/CCR5−/− recipients’ expressed high levels of VCAM-1 and MMP7 mRNA that was associated with high serum titers of DSA. At rejection in wild type and CD8−/−/CCR5−/− recipients, kidney allografts also expressed genes associated with NK cell (Sh2d1B1 and MYBL1) but not with T cell (CXCR6) activity during inflammation. High levels of perforin and granzyme B mRNA expression in kidney allografts peaked on day 6 post-transplant in all recipients. NK cell depletion in CD8−/−/CCR5−/− recipients reduced this expression to background levels and promoted long-term survival of 40% of kidney allografts. These results support a role for NK cells in increasing inflammation during antibody-mediated kidney allograft injury and rejection.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.196.Supp.140.17
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2016
detail.hit.zdb_id:
1475085-5
