Quantitative assessment of T cell repertoire recovery after hematopoietic stem cell transplantation

JWJ Van Heijst, I Ceberio, LB Lipuma, DW Samilo… - Nature medicine, 2013 - nature.com
JWJ Van Heijst, I Ceberio, LB Lipuma, DW Samilo, GD Wasilewski, AMR Gonzales…
Nature medicine, 2013nature.com
Delayed T cell recovery and restricted T cell receptor (TCR) diversity after allogeneic
hematopoietic 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 …
Abstract
Delayed T cell recovery and restricted T cell receptor (TCR) diversity after allogeneic hematopoietic 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.
nature.com