期刊
JCI INSIGHT
卷 6, 期 13, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.149080
关键词
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资金
- US NIH [R35 HL135795, R01 HL123904, R01 380HL118281, R01 HL128425, R01 HL132071]
- Edward P. Evans Foundation
- Italian Society of Hematology
- Fondation ARC pour la Recherche sur le Cancer
- Philippe Foundation Inc
- American-Italian Cancer Foundation
- VeloSano Pilot Award
- Vera and Joseph Dresner Foundation-MDS
TCR repertoire diversification is crucial for successful immune reconstitution after allo-HCT. Analyses of deep TCR V beta sequencing revealed that rarefied and hyperexpanded clonotypic patterns are hallmarks of T cell reconstitution, influenced by donor and pretransplant TCR diversity. The expansion of pathogen- and tumor-associated clonotypes was predominant in the late post-allo-HCT phase, while autoreactive clones were more expanded in cases of graft-versus-host disease.
TCR repertoire diversification constitutes a foundation for successful immune reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT). Deep TCR V beta sequencing of 135 serial specimens from a cohort of 35 allo-HCT recipients/donors was performed to dissect posttransplant TCR architecture and dynamics. Paired analysis of clonotypic repertoires showed a minimal overlap with donor expansions. Rarefied and hyperexpanded clonotypic patterns were hallmarks of T cell reconstitution and influenced clinical outcomes. Donor and pretransplant TCR diversity as well as divergence of class I human leukocyte antigen genotypes were major predictors of recipient TCR repertoire recovery. Complementary determining region 3-based specificity spectrum analysis indicated a predominant expansion of pathogen- and tumor-associated clonotypes in the late post-allo-HCT phase, while autoreactive clones were more expanded in the case of graft-versus-host disease occurrence. These findings shed light on post-allo-HCT adaptive immune reconstitution processes and possibly help in tracking alloreactive responses.
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