Date: Sunday, May 3, 2015
Session Time: 4:00pm-5:30pm
Presentation Time: 4:00pm-4:12pm
Location: Room 118-AB
Antibody-mediated acute and chronic graft injury remains a major cause of renal allograft loss. Mechanisms underlying these injuries remain unclear due in part to the absence of relevant preclinical models. We have reported that MHC-mismatched renal allograft rejection in CCR5-/- recipients requires donor-specific antibody, shares histopathological features with AMR of clinical renal grafts, and is accompanied by CD8 T cell graft infiltration. This study investigated the role of CD8 T cells in the renal allograft rejection by crossing CD8-/- and CCR5-/- mice to generate B6.CD8-/-CCR5-/- mice. A/J (H-2a) kidneys were transplanted to wild-type (WT) C57BL/6 (H-2b), B6.CCR5-/- and B6.CD8-/-CCR5-/- mice. Whereas 60% of renal allografts survived over 90 days in WT recipients, CCR5-/- recipients rejected the allografts within 24 days with a mean survival of 16.75 +/- 5.7 days and CD8-/-CCR5-/- recipients rejected the allografts with a mean survival of 27.33 +/-13.67 days. To investigate potential factors underlying antibody mediated injury of the renal allografts, serum and allografts were recovered from WT C57BL/6, CCR5-/- and CD8-/-/CCR5-/- recipients at days 3, 6, and 14 post-transplant and at the time of the rejection. DSA titers in WT allograft recipients were lower at the peak on day 14 post-transplant than those in CCR5-/- allograft recipients (2932 +/- 1844 vs 8192 +/- 6345) but were higher at this time in CD8-/-CCR5-/- allograft recipients (30877 +/- 27641). A/J renal allografts from WT B6 and CCR5-/-recipients contained diffuse interstitial CD3+ T cell infiltrates by day 3 and these infiltrates increased on days 6 and 14. Although allografts from CD8-/-/CCR5-/- recipients had less intense CD3+ T cell infiltrates on day 3, these infiltrates increased and were diffuse and intense by days 6 and 14. Expression of CXCL1, CXCL2, CCL2, IFN-γ, perforin appeared in allografts early after transplant in all recipients and then decreased, but levels were lower in allografts from WT recipients. In contrast, allograft expression of MMP7 mRNA was low at early times post-transplant but increased with the increasing DSA titers in CCR5-/- and CD8-/-/CCR5-/- recipients but not in WT recipients. These results indicate that infiltrating CD8 T cells contribute to rejection of renal allografts in CCR5-/- recipients, but are not required for AMR in this model.
To cite this abstract in AMA style:Kohei N, Tanaka T, Tsuda H, Dvorina N, Tanabe K, Baldwin W, Fairchild R. Antibody-Mediated Rejection of Renal Allografts by CCR5-/- Mice Does Not Require CD8 T Cells [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/antibody-mediated-rejection-of-renal-allografts-by-ccr5-mice-does-not-require-cd8-t-cells/. Accessed January 25, 2021.
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