Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT
Abstract KIR are mainly expressed on NK cells and to a lesser extent on T lymphocytes. Although the KIR NK cell repertoire was well explored in haploidentical Hematopoietic Stem Cell Transplantation (HSCT), KIR T cell compartment remains to be investigated in this context. In this study, the investi...
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Nature Portfolio
2021
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oai:doaj.org-article:6d647b4ddb4e4b30bc075d7c4404c2912021-12-02T16:35:28ZDeciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT10.1038/s41598-021-95245-72045-2322https://doaj.org/article/6d647b4ddb4e4b30bc075d7c4404c2912021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95245-7https://doaj.org/toc/2045-2322Abstract KIR are mainly expressed on NK cells and to a lesser extent on T lymphocytes. Although the KIR NK cell repertoire was well explored in haploidentical Hematopoietic Stem Cell Transplantation (HSCT), KIR T cell compartment remains to be investigated in this context. In this study, the investigation of NK receptors on T lymphocytes during immune reconstitution after T-cell-replete haploidentical HSCT with Post-Transplant Cyclophosphamide (PTCy) has shown a significant increase of KIR2DL2/3+ T cell frequency at day 25. This was especially observed at day 30 in recipients who relapsed. IL-15 but not IL-12 increased in vitro KIR+ T cell expansion suggesting that the raised IL-15 serum concentration observed after PTCy in haploidentical HSCT might increase KIR+ T cell frequency. Moreover, investigations from healthy blood donors showed a higher inhibiting effect of KIR2DL3 on CMV specific T cell response against allogeneic than autologous C1+ target cells. The association of KIR+ T cell subset with relapse may suggest that inhibitory KIR2DL2/3 limit anti-leukemic effect of specific T lymphocytes at this early step of immune reconstitution. Further phenotypic and mechanistic investigations on this cell subset from a broader cohort of HSCT recipients should clarify its potential implication in relapse occurrence. Our results demonstrate that KIR-HLA interactions known to modulate NK cell functions also modulate T cell immune responses in the context of allogeneic HSCT.Gaëlle DavidCatherine WillemNolwenn LegrandZakia DjaoudPierre MérieauAlexandre WalencikThierry GuillaumeKatia GagnePatrice ChevallierChristelle RetièreNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
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Medicine R Science Q Gaëlle David Catherine Willem Nolwenn Legrand Zakia Djaoud Pierre Mérieau Alexandre Walencik Thierry Guillaume Katia Gagne Patrice Chevallier Christelle Retière Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT |
| description |
Abstract KIR are mainly expressed on NK cells and to a lesser extent on T lymphocytes. Although the KIR NK cell repertoire was well explored in haploidentical Hematopoietic Stem Cell Transplantation (HSCT), KIR T cell compartment remains to be investigated in this context. In this study, the investigation of NK receptors on T lymphocytes during immune reconstitution after T-cell-replete haploidentical HSCT with Post-Transplant Cyclophosphamide (PTCy) has shown a significant increase of KIR2DL2/3+ T cell frequency at day 25. This was especially observed at day 30 in recipients who relapsed. IL-15 but not IL-12 increased in vitro KIR+ T cell expansion suggesting that the raised IL-15 serum concentration observed after PTCy in haploidentical HSCT might increase KIR+ T cell frequency. Moreover, investigations from healthy blood donors showed a higher inhibiting effect of KIR2DL3 on CMV specific T cell response against allogeneic than autologous C1+ target cells. The association of KIR+ T cell subset with relapse may suggest that inhibitory KIR2DL2/3 limit anti-leukemic effect of specific T lymphocytes at this early step of immune reconstitution. Further phenotypic and mechanistic investigations on this cell subset from a broader cohort of HSCT recipients should clarify its potential implication in relapse occurrence. Our results demonstrate that KIR-HLA interactions known to modulate NK cell functions also modulate T cell immune responses in the context of allogeneic HSCT. |
| format |
article |
| author |
Gaëlle David Catherine Willem Nolwenn Legrand Zakia Djaoud Pierre Mérieau Alexandre Walencik Thierry Guillaume Katia Gagne Patrice Chevallier Christelle Retière |
| author_facet |
Gaëlle David Catherine Willem Nolwenn Legrand Zakia Djaoud Pierre Mérieau Alexandre Walencik Thierry Guillaume Katia Gagne Patrice Chevallier Christelle Retière |
| author_sort |
Gaëlle David |
| title |
Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT |
| title_short |
Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT |
| title_full |
Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT |
| title_fullStr |
Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT |
| title_full_unstemmed |
Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT |
| title_sort |
deciphering the biology of kir2dl3+ t lymphocytes that are associated to relapse in haploidentical hsct |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/6d647b4ddb4e4b30bc075d7c4404c291 |
| work_keys_str_mv |
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| _version_ |
1718383695890481152 |