Monocyte derived dendritic cells impair early graft function following allogeneic islet transplantation

Chow, KV; Carrington, EM; Zhan, Y; Lew, AM; Sutherland, RM

Author(s): Chow, KV; Carrington, EM; Zhan, Y; Lew, AM; Sutherland, RM;
Details: Publication Year 2017-10-13,Volume 26,Issue #2,Page 319-326
Journal Title: Cell Transplantation
Publication Type: Journal Article
Abstract: Islet transplantation can cure type 1 diabetes, but is limited by lack of donor organs and early graft dysfunction, such that many patients require multiple transplants to achieve insulin independence. Monocyte derived dendritic cells (moDCs) arise during inflammation and allograft encounters where they can promote various innate and adaptive immune responses. To determine whether moDCs impair early graft function following allogeneic islet transplantation, we transplanted MHC-mismatched BALB/c (H-2d) islets into diabetic C57BL/6-CCR2.DTR recipients (H-2b), treated with either saline (control) or diphtheria toxin (DT) to deplete moDCs. Graft function was assessed by blood glucose (BG) measurement. DT resulted in specific depletion of graft site moDCs post-transplant. Despite equivalent pre-transplant BG levels (27.0 +/- 1.3 vs 29.6 +/- 1.1 mM, ns), DT recipients achieved lower post-transplant BG levels and better rates of normoglycemia than control recipients (11.0 +/- 1.9 vs 19.1 +/- 1.4 mM, p = 0.004) at 1 day post-transplant in diabetic recipients. When a suboptimal donor dose of 200 islets were transplanted, DT-induced moDC depletion resulted in normoglycemia in 78% compared to 25% of control recipients (p = 0.03). As well as amelioration of graft dysfunction in the immediate peri-transplant period, prolonged DT administration (15 days post-transplant) resulted in improved graft survival (21 vs 11 days, p = 0.005). moDCs impair early graft function post-allogeneic islet transplantation. moDC depletion may allow for improved early graft function, permit transplantation with lower islet masses, and enhance graft survival.
Publisher: Ingenta
Research Division(s): Immunology
PubMed ID: 27743446
Link To PubMed Central Version: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657768/
Publisher's Version: https://doi.org/10.3727/096368916X693482
NHMRC Grants: NHMRC/1037321, NHMRC/1043414, NHMRC/1080321, NHMRC/1105209,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2017-05-26 02:39:17

Last Modified: 2018-07-05 08:50:42