NK and T cell repertoire is established early after allogeneic HSCT and is profoundly imprinted by CMV reactivation.

Autor:	Schäfer A; Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva Center for Inflammation Research, Geneva University Hospitals, Swaziland., Calderin Sollet Z; Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva Center for Inflammation Research, Geneva University Hospitals, Switzerland., Hervé MP; Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva Center for Inflammation Research, Geneva University Hospitals, Switzerland., Buhler S; Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva Center for Inflammation Research, Geneva University Hospitals, Switzerland., Ferrari-Lacraz S; Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva Center for Inflammation Research, Geneva University Hospitals, Switzerland., Norman PJ; Department of Biomedical Informatics and Department of Immunology and Microbiology, University of Colorado School of Medicine, United States., Kichula KM; Department of Biomedical Informatics and Department of Immunology and Microbiology, University of Colorado School of Medicine, United States., Farias TDJ; The University of North Carolina at Charlotte, United States., Masouridi-Levrat S; Geneva University Hospitals, Geneva, Switzerland., Mamez AC; Geneva University Hospitals, Genève 14, Switzerland., Pradier A; Geneva University Hospitals and University of Geneva., Simonetta F; Geneva University Hospitals and Geneva Medical School, Genève, Switzerland., Chalandon Y; University Hospital of Geneva, Geneva, Switzerland., Villard J Prof; Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva Center for Inflammation Research, Geneva University Hospitals, Switzerland.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Jul 24. Date of Electronic Publication: 2024 Jul 24.
DOI:	10.1182/bloodadvances.2024013117
Abstrakt:	Besides genetic influences, non-genetic factors such as graft-versus-host disease (GvHD) and viral infections have been shown as important shapers of the immune reconstitution and diversification processes after hematopoietic stem cell transplantation (HSCT). However, the differential susceptibility to immune modulation by non-genetic factors is not fully understood. We determined to follow the reconstitution of the T cell receptor (TCR) repertoire through immune-sequencing, of natural killer (NK) cells using a 35-marker spectral flow cytometry panel, and in relation to clinical events. Longitudinal investigation was performed on samples derived from 54 HSCT recipients during the first-year post-HSCT. We confirmed a significant contraction in TCR repertoire diversity with a remarkable stability over time. CMV reactivation had the ability to significantly change TCR repertoire clonality and composition, with a long-lasting imprint. Our data further revealed skewing of NK cell reconstitution in CMV reactivated recipients, with an increased frequency of KIR2DL2L3S2+ adaptive, cytolytic and functional CD107a+ NK cells concomitant with a reduced pool of NKG2A+ NK cells. We provided support that CMV might act as one of the more important driver of peripheral homeostatic proliferation of circulating specific T and NK cells, which can be viewed as a compensatory mechanism to establish a new peripheral repertoire. (Copyright © 2024 American Society of Hematology.)
Databáze:	MEDLINE
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