Discrimination of Anti-Donor Response in Allogeneic Transplantation Using an Alloreactive T-Cell Detection Assay

Bibliographic Details
Title: Discrimination of Anti-Donor Response in Allogeneic Transplantation Using an Alloreactive T-Cell Detection Assay
Authors: Ryosuke Arata, Naoki Tanimine, Akhmet Seidakhmetov, Kentaro Ide, Yuka Tanaka, Hideki Ohdan
Source: Transplant International, Vol 38 (2025)
Publisher Information: Frontiers Media S.A., 2025.
Publication Year: 2025
Collection: LCC:Specialties of internal medicine
Subject Terms: immune monitoring, allogeneic transplantation, alloreactive T-cell, rejection, tolerance, Specialties of internal medicine, RC581-951
More Details: Understanding donor-reactive T-cell behavior post-transplantation is challenging owing to the rarity and diversity of these cells. Here, we aimed to evaluate the relevance of an assay for rapidly detecting alloreactive T cells in a mouse transplantation model. After 18 h of one-way mixed lymphocyte reaction (MLR) culture with pre-activated donor-derived stimulators, CD4+ and CD8+ donor-reactive T cells were identified by CD154 and CD137 expression, respectively. Using full MHC mismatched mouse skin transplant models, we observed an increased donor-reactive T-cell proportion by direct presentation with elevated interferon gamma and granzyme B production 7 days post-transplantation, before graft rejection. Immunosuppression with CTLA-4 IgG and anti-CD154 antibody varied depending on donor-recipient strain combinations. On day 7, donor-reactive CD8+ T-cell proportions were lower in the tolerance model (BALB/c to C3H/HeJ) than in the rejection model (BALB/c to C57BL/6); conventional proliferation readout after 4 days of MLR could not distinguish these responses. Overall, although the conventional readout for evaluating T-cell proliferation following an MLR quantifies the precursor frequency of alloreactive T cells, the assay reported herein assesses T-cell activation markers after a short-term MLR to characterize immediate immune status. These findings offer a promising tool to elucidate immune responses post-transplantation.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1432-2277
Relation: https://www.frontierspartnerships.org/articles/10.3389/ti.2025.13879/full; https://doaj.org/toc/1432-2277
DOI: 10.3389/ti.2025.13879
Access URL: https://doaj.org/article/9a5107ac4a9d4a04aac857695bf3c412
Accession Number: edsdoj.9a5107ac4a9d4a04aac857695bf3c412
Database: Directory of Open Access Journals
More Details
ISSN:14322277
DOI:10.3389/ti.2025.13879
Published in:Transplant International
Language:English