期刊
TRANSPLANT INFECTIOUS DISEASE
卷 16, 期 6, 页码 930-940出版社
WILEY
DOI: 10.1111/tid.12318
关键词
HLA-A*2402-restricted cytomegalovirus-specific cytotoxic T cells; T cell receptor-; single-cell analysis; clone monitoring; chimerism analysis; CTL; CMV
资金
- Health and Labor Science Research Grant (Research on Allergic Disease and Immunology) from the Ministry of Health, Labour and Welfare of Japan
- Japanese Kidney Association through its promotion funds from KEIRIN RACE
- Research Award for a Jichi Medical University Graduate Student
- Japan Herpes Virus Infection Forum Scholarship Award
BackgroundCytomegalovirus (CMV)-specific CD8(+) cytotoxic T lymphocytes (CMV-CTLs) play a crucial role in preventing CMV disease. However, the actual in vivo dynamics of CMV-CTL clones after allogeneic hematopoietic stem cell transplantation (alloHCT) are still unclear. MethodsUsing a single-cell T-cell receptor repertoire analysis, we monitored clones and chimerism of CMV-CTLs in 3 CMV-seropositive alloHCT recipients from CMV-seronegative donors, with or without CMV reactivation. ResultsNearly all of the CMV-CTLs during follow-up were CD45RA(-)CCR7(-) effector memory/CD45RA(+)CCR7(-) effector T cells, and were highly matured. In each case, the use of BV gene families was restricted, especially in BV5, 7, 28, and 29. Although no common predominant CMV-CTL clones were found, several shared motifs of complementarity-determining region-3 were identified among the 3 cases; QGA in all, TGE and TDT in Case 1 and Case 2, and RDRG in Case 2 and Case 3. In all cases, CMV-CTL clones that were detected for the first time after alloHCT persisted as the dominant clones. In Case 1, without CMV reactivation, recipient-derived CMV-CTLs exclusively persisted as a dominant clone, while all CMV-CTLs in the other 2 cases, with CMV reactivation, were donor derived. ConclusionClone monitoring and chimerism analyses should help to further clarify novel aspects of immuno-reconstitution after alloHCT.
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