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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 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.
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Contributor : Elizabeth Bernardo Connect in order to contact the contributor
Submitted on : Monday, August 9, 2021 - 7:54:13 AM
Last modification on : Wednesday, April 27, 2022 - 3:59:33 AM
Long-term archiving on: : Wednesday, November 10, 2021 - 6:15:58 PM


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Gaëlle David, Catherine Willem, Nolwenn Legrand, Zakia Djaoud, Pierre Mérieau, et al.. Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT. Scientific Reports, Nature Publishing Group, 2021, 11 (1), pp.15782. ⟨10.1038/s41598-021-95245-7⟩. ⟨inserm-03317982⟩



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