期刊
NATURE MEDICINE
卷 19, 期 3, 页码 372-377出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3100
关键词
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资金
- Netherlands Organisation for Scientific Research (NWO)
- Asociacion Espanola Contra el Cancer (AECC)
- US National Institutes of Health (NIH) [HL069929, CA023766, AI080455, AI100288, AI101406, AI042135, AI039031]
- Tow Foundation
- US Department of Defense (USAMRAA Award) [W81XWH-09-1-0294]
- Radiation Effects Research Foundation (RERF-NIAID)
- Lymphoma Foundation
- Alex's Lemonade Stand
- Geoffrey Beene Cancer Research Center at Memorial Sloan-Kettering Cancer Center
- Susan and Peter Solomon Divisional Genomics Program
- Translational and Integrative Medicine Research Fund of Memorial Sloan-Kettering Cancer Center
- Cycle for Survival
- New York Community Trust
- When Everyone Survives
- Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center
Delayed T cell recovery and restricted T cell receptor (TCR) diversity after allogeneic hematapoietic stem cell transplantation (allo-HSCT) are associated with increased risks of infection and cancer relapse. Technical challenges have limited faithful measurement of TCR diversity after allo-HSCT. Here we combined 5' rapid amplification of complementary DNA ends PCR with deep sequencing to quantify TCR diversity in 28 recipients of allo-HSCT using a single oligonucleotide pair. Analysis of duplicate blood samples confirmed that we accurately determined the frequency of individual TCRs. After 6 months, cord blood-graft recipients approximated the TCR diversity of healthy individuals, whereas recipients of T cell-depleted peripheral-blood stem cell grafts had 28-fold and 14-fold lower CD4(+) and CD8(+) T cell diversities, respectively. After 12 months, these deficiencies had improved for the CD4(+) but not the CD8(+) T cell compartment. Overall, this method provides unprecedented views of T cell repertoire recovery after allo-HSCT and may identify patients at high risk of infection or relapse.
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