title: Quantitative assessment of T cell repertoire recovery after hematopoietic stem cell transplantation.
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.
authors: Immunology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. vanheijj@mskcc.org
authors: Jeroen W J
authors: JW
authors: van Heijst
authors: Izaskun
authors: I
authors: Ceberio
authors: Lauren B
authors: LB
authors: Lipuma
authors: Dane W
authors: DW
authors: Samilo
authors: Gloria D
authors: GD
authors: Wasilewski
authors: Anne Marie R
authors: AM
authors: Gonzales
authors: Jimmy L
authors: JL
authors: Nieves
authors: Marcel R M
authors: MR
authors: van den Brink
authors: Miguel A
authors: MA
authors: Perales
authors: Eric G
authors: EG
authors: Pamer
mesh_terms: D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014644:Genetic Variation; D019337:Hematologic Neoplasms / Q000097:blood / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012008:Recurrence; D017422:Sequence Analysis, DNA
chemical_list: D011948:Receptors, Antigen, T-Cell