quantitative assessment of t cell repertoire recovery after hematopoietic stem cell transplantation - nature medicine
2016-06-24
nature medicine,2015
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.