Discrimination of Anti-Donor Response in Allogeneic Transplantation Using an Alloreactive T-Cell Detection Assay
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...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Transplant International |
| Subjects: | |
| Online Access: | https://www.frontierspartnerships.org/articles/10.3389/ti.2025.13879/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832583857019289600 |
|---|---|
| author | Ryosuke Arata Naoki Tanimine Akhmet Seidakhmetov Kentaro Ide Yuka Tanaka Hideki Ohdan |
| author_facet | Ryosuke Arata Naoki Tanimine Akhmet Seidakhmetov Kentaro Ide Yuka Tanaka Hideki Ohdan |
| author_sort | Ryosuke Arata |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9a5107ac4a9d4a04aac857695bf3c412 |
| institution | Kabale University |
| issn | 1432-2277 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Transplant International |
| spelling | doaj-art-9a5107ac4a9d4a04aac857695bf3c4122025-01-28T04:10:55ZengFrontiers Media S.A.Transplant International1432-22772025-01-013810.3389/ti.2025.1387913879Discrimination of Anti-Donor Response in Allogeneic Transplantation Using an Alloreactive T-Cell Detection AssayRyosuke ArataNaoki TanimineAkhmet SeidakhmetovKentaro IdeYuka TanakaHideki OhdanUnderstanding 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.https://www.frontierspartnerships.org/articles/10.3389/ti.2025.13879/fullimmune monitoringallogeneic transplantationalloreactive T-cellrejectiontolerance |
| spellingShingle | Ryosuke Arata Naoki Tanimine Akhmet Seidakhmetov Kentaro Ide Yuka Tanaka Hideki Ohdan Discrimination of Anti-Donor Response in Allogeneic Transplantation Using an Alloreactive T-Cell Detection Assay Transplant International immune monitoring allogeneic transplantation alloreactive T-cell rejection tolerance |
| title | Discrimination of Anti-Donor Response in Allogeneic Transplantation Using an Alloreactive T-Cell Detection Assay |
| title_full | Discrimination of Anti-Donor Response in Allogeneic Transplantation Using an Alloreactive T-Cell Detection Assay |
| title_fullStr | Discrimination of Anti-Donor Response in Allogeneic Transplantation Using an Alloreactive T-Cell Detection Assay |
| title_full_unstemmed | Discrimination of Anti-Donor Response in Allogeneic Transplantation Using an Alloreactive T-Cell Detection Assay |
| title_short | Discrimination of Anti-Donor Response in Allogeneic Transplantation Using an Alloreactive T-Cell Detection Assay |
| title_sort | discrimination of anti donor response in allogeneic transplantation using an alloreactive t cell detection assay |
| topic | immune monitoring allogeneic transplantation alloreactive T-cell rejection tolerance |
| url | https://www.frontierspartnerships.org/articles/10.3389/ti.2025.13879/full |
| work_keys_str_mv | AT ryosukearata discriminationofantidonorresponseinallogeneictransplantationusinganalloreactivetcelldetectionassay AT naokitanimine discriminationofantidonorresponseinallogeneictransplantationusinganalloreactivetcelldetectionassay AT akhmetseidakhmetov discriminationofantidonorresponseinallogeneictransplantationusinganalloreactivetcelldetectionassay AT kentaroide discriminationofantidonorresponseinallogeneictransplantationusinganalloreactivetcelldetectionassay AT yukatanaka discriminationofantidonorresponseinallogeneictransplantationusinganalloreactivetcelldetectionassay AT hidekiohdan discriminationofantidonorresponseinallogeneictransplantationusinganalloreactivetcelldetectionassay |