Differential Role of B Cells and IL-17 Versus IFN-γ During Early and Late Rejection of Pig Islet Xenografts in Mice.

Published

Journal Article

Xenogeneic islet transplantation is an emerging therapeutic option for diabetic patients. However, immunological tolerance to xenogeneic islets remains a challenge.The current study used a pig-to-mouse discordant xenogeneic islet transplant model to examine antidonor xenogeneic immune responses during early and late rejection and to determine experimental therapeutic interventions that promote durable pig islet xenograft survival.We found that during early acute rejection of pig islet xenografts, the rejecting hosts exhibited a heavy graft infiltration with B220 B cells and a robust antipig antibody production. In addition, early donor-stimulated IL-17 production, but not IFN-γ production, dominated during early acute rejection. Recipient treatment with donor apoptotic 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide-treated splenocytes significantly inhibited antidonor IL-17 response, and when combined with B cell depletion and a short course of rapamycin led to survival of pig islet xenografts beyond 100 days in approximately 65% recipients. Interestingly, treated recipients in this model experienced late rejection between 100 and 200 days posttransplant, which coincided with B cell reconstitution and an ensuing emergence of a robust antidonor IFN-γ, but not IL-17, response.These findings reveal that early and late rejection of pig islet xenografts may be dominated by different immune responses and that maintenance of long-term xenogeneic tolerance will require strategies that target the temporal sequence of antixenogeneic immune responses.

Full Text

Duke Authors

Cited Authors

  • Kang, HK; Wang, S; Dangi, A; Zhang, X; Singh, A; Zhang, L; Rosati, JM; Suarez-Pinzon, W; Deng, X; Chen, X; Thorp, EB; Hering, BJ; Miller, SD; Luo, X

Published Date

  • August 2017

Published In

Volume / Issue

  • 101 / 8

Start / End Page

  • 1801 - 1810

PubMed ID

  • 27893617

Pubmed Central ID

  • 27893617

Electronic International Standard Serial Number (EISSN)

  • 1534-6080

International Standard Serial Number (ISSN)

  • 0041-1337

Digital Object Identifier (DOI)

  • 10.1097/TP.0000000000001489

Language

  • eng