Expansion of CD45RA−FOXP3++ regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation
Abstract Objectives Simultaneous transplantation of a solid organ and bone marrow from the same donor is a possible means of achieving transplant tolerance. Here, we attempted to identify biomarkers that indicate transplant tolerance for discontinuation of immunosuppressants in combined kidney and b...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-01-01
|
| Series: | Clinical & Translational Immunology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cti2.1325 |
| _version_ | 1831769797666275328 |
|---|---|
| author | Yeongbeen Kwon Kyo Won Lee You Min Kim Hyojun Park Min Kyung Jung Young Joon Choi Jin Kyung Son JuHee Hong Su‐Hyung Park Ghee Young Kwon Heejin Yoo Kyunga Kim Sung Joo Kim Jae Berm Park Eui‐Cheol Shin |
| author_facet | Yeongbeen Kwon Kyo Won Lee You Min Kim Hyojun Park Min Kyung Jung Young Joon Choi Jin Kyung Son JuHee Hong Su‐Hyung Park Ghee Young Kwon Heejin Yoo Kyunga Kim Sung Joo Kim Jae Berm Park Eui‐Cheol Shin |
| author_sort | Yeongbeen Kwon |
| collection | DOAJ |
| description | Abstract Objectives Simultaneous transplantation of a solid organ and bone marrow from the same donor is a possible means of achieving transplant tolerance. Here, we attempted to identify biomarkers that indicate transplant tolerance for discontinuation of immunosuppressants in combined kidney and bone marrow transplantation (CKBMT). Methods Conventional kidney transplant (KT) recipients (n = 20) and CKBMT recipients (n = 6) were included in this study. We examined various immunological parameters by flow cytometry using peripheral blood mononuclear cells (PBMCs), including the frequency and phenotype of regulatory T (Treg) cell subpopulations. We also examined the suppressive activity of the Treg cell population in the setting of mixed lymphocyte reaction (MLR) with or without Treg cell depletion. Results Among six CKBMT recipients, three successfully discontinued immunosuppressants (tolerant group) and three could not (non‐tolerant group). The CD45RA−FOXP3++ Treg cell subpopulation was expanded in CKBMT recipients compared to conventional kidney transplant patients, and this was more obvious in the tolerant group than the non‐tolerant group. In addition, high suppressive activity of the Treg cell population was observed in the tolerant group. The ratio of CD45RA−FOXP3++ Treg cells to CD45RA−FOXP3+ cells indicated good discrimination between the tolerant and non‐tolerant groups. Conclusion Thus, our findings propose a biomarker that can distinguish CKBMT patients who achieve transplant tolerance and are eligible for discontinuation of immunosuppressants and may provide insight into tolerance mechanisms in CKBMT. |
| first_indexed | 2024-12-22T07:28:02Z |
| format | Article |
| id | doaj.art-276e808d649b4ac48fbc28b12477e8f1 |
| institution | Directory Open Access Journal |
| issn | 2050-0068 |
| language | English |
| last_indexed | 2024-12-22T07:28:02Z |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical & Translational Immunology |
| spelling | doaj.art-276e808d649b4ac48fbc28b12477e8f12022-12-21T18:34:06ZengWileyClinical & Translational Immunology2050-00682021-01-01108n/an/a10.1002/cti2.1325Expansion of CD45RA−FOXP3++ regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantationYeongbeen Kwon0Kyo Won Lee1You Min Kim2Hyojun Park3Min Kyung Jung4Young Joon Choi5Jin Kyung Son6JuHee Hong7Su‐Hyung Park8Ghee Young Kwon9Heejin Yoo10Kyunga Kim11Sung Joo Kim12Jae Berm Park13Eui‐Cheol Shin14Samsung Advanced Institute for Health Sciences & Technology (SAIHST) Graduate School Department of Health Sciences & Technology Sungkyunkwan University Seoul KoreaTransplantation Research Center Samsung Medical Center Samsung Biomedical Research Institute Seoul KoreaGraduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology (KAIST) Daejeon KoreaTransplantation Research Center Samsung Medical Center Samsung Biomedical Research Institute Seoul KoreaGraduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology (KAIST) Daejeon KoreaGraduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology (KAIST) Daejeon KoreaTransplantation Research Center Samsung Medical Center Samsung Biomedical Research Institute Seoul KoreaTransplantation Research Center Samsung Medical Center Samsung Biomedical Research Institute Seoul KoreaGraduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology (KAIST) Daejeon KoreaDepartment of Pathology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul KoreaStatistics and Data Center Samsung Medical Center Research Institute for Future Medicine Seoul KoreaStatistics and Data Center Samsung Medical Center Research Institute for Future Medicine Seoul KoreaTransplantation Research Center Samsung Medical Center Samsung Biomedical Research Institute Seoul KoreaSamsung Advanced Institute for Health Sciences & Technology (SAIHST) Graduate School Department of Health Sciences & Technology Sungkyunkwan University Seoul KoreaGraduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology (KAIST) Daejeon KoreaAbstract Objectives Simultaneous transplantation of a solid organ and bone marrow from the same donor is a possible means of achieving transplant tolerance. Here, we attempted to identify biomarkers that indicate transplant tolerance for discontinuation of immunosuppressants in combined kidney and bone marrow transplantation (CKBMT). Methods Conventional kidney transplant (KT) recipients (n = 20) and CKBMT recipients (n = 6) were included in this study. We examined various immunological parameters by flow cytometry using peripheral blood mononuclear cells (PBMCs), including the frequency and phenotype of regulatory T (Treg) cell subpopulations. We also examined the suppressive activity of the Treg cell population in the setting of mixed lymphocyte reaction (MLR) with or without Treg cell depletion. Results Among six CKBMT recipients, three successfully discontinued immunosuppressants (tolerant group) and three could not (non‐tolerant group). The CD45RA−FOXP3++ Treg cell subpopulation was expanded in CKBMT recipients compared to conventional kidney transplant patients, and this was more obvious in the tolerant group than the non‐tolerant group. In addition, high suppressive activity of the Treg cell population was observed in the tolerant group. The ratio of CD45RA−FOXP3++ Treg cells to CD45RA−FOXP3+ cells indicated good discrimination between the tolerant and non‐tolerant groups. Conclusion Thus, our findings propose a biomarker that can distinguish CKBMT patients who achieve transplant tolerance and are eligible for discontinuation of immunosuppressants and may provide insight into tolerance mechanisms in CKBMT.https://doi.org/10.1002/cti2.1325chimerismcombined kidney and bone marrow transplantationregulatory T cellstolerance |
| spellingShingle | Yeongbeen Kwon Kyo Won Lee You Min Kim Hyojun Park Min Kyung Jung Young Joon Choi Jin Kyung Son JuHee Hong Su‐Hyung Park Ghee Young Kwon Heejin Yoo Kyunga Kim Sung Joo Kim Jae Berm Park Eui‐Cheol Shin Expansion of CD45RA−FOXP3++ regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation Clinical & Translational Immunology chimerism combined kidney and bone marrow transplantation regulatory T cells tolerance |
| title | Expansion of CD45RA−FOXP3++ regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation |
| title_full | Expansion of CD45RA−FOXP3++ regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation |
| title_fullStr | Expansion of CD45RA−FOXP3++ regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation |
| title_full_unstemmed | Expansion of CD45RA−FOXP3++ regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation |
| title_short | Expansion of CD45RA−FOXP3++ regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation |
| title_sort | expansion of cd45ra foxp3 regulatory t cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation |
| topic | chimerism combined kidney and bone marrow transplantation regulatory T cells tolerance |
| url | https://doi.org/10.1002/cti2.1325 |
| work_keys_str_mv | AT yeongbeenkwon expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation AT kyowonlee expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation AT youminkim expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation AT hyojunpark expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation AT minkyungjung expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation AT youngjoonchoi expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation AT jinkyungson expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation AT juheehong expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation AT suhyungpark expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation AT gheeyoungkwon expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation AT heejinyoo expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation AT kyungakim expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation AT sungjookim expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation AT jaebermpark expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation AT euicheolshin expansionofcd45rafoxp3regulatorytcellsisassociatedwithimmunetoleranceinpatientswithcombinedkidneyandbonemarrowtransplantation |