A broad T-cell repertoire diversity and an efficient thymic function indicate a favorable long-term immune reconstitution after cord blood stem cell transplantation

被引:155
作者
Talvensarri, K
Clave, E
Douay, C
Rabian, C
Garderet, L
Busson, M
Garnier, F
Douek, D
Gluckman, E
Charron, D
Toubert, A
机构
[1] Hop St Louis, APHP, Serv Hematol Greffe de Moelle, F-75475 Paris 10, France
[2] Inst Univ Hematol, Lab Immunol & Histocompatibil, INSERM U396, Paris, France
[3] NCI, Dept Expt Transplantat & Immunol, NIH, Bethesda, MD 20892 USA
[4] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA
关键词
D O I
10.1182/blood.V99.4.1458
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cord blood (CB) is used increasingly as a source of hematopoietic stem cells because of a lower risk of acute and chronic graft-versus-host disease (GVHD). However, there is some concern regarding the ability to adequately reconstitute host immune response due to the immaturity and naivety of CB T cells. This study was designed to evaluate T-cell reconstitution using combined approaches of phenotyping, analysis of alphabeta T-cell receptor (TCR) diversity, and assessment of ex vivo thymic function by measuring TCR rearrangement excision circles (TRECs). Ten patients who underwent CB transplantation for high-risk hematologic disorders were compared to a reference group of 19 age and GVHD-matched patients who underwent transplantation with non-T cell-depleted bone marrow from an HILA-Identical sibling donor. TREC values correlated with the relative number of naive T cells and with TCR repertoire polyclonality. During the first year after transplantation, TCR repertoires were highly abnormal and TREC values low in both groups.Notably, 2 years after transplantation onward TREC values as well as TCR diversity were higher In CB recipients than in recipients of bone marrow transplants. These data Indicate an efficient thymic regeneration pathway from CB lymphoid progenitors despite the low number of cells Infused compared to bone marrow, arguing for a complete clinical Immune recovery after CB transplantation. (C) 2002 by The American Society of Hematology.
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页码:1458 / 1464
页数:7
相关论文
共 39 条
[1]   Immunological reconstitution and correlation of circulating serum inflammatory mediators/cytokines with the incidence of acute graft-versus-host disease during the first 100 days following unrelated umbilical cord blood transplantation [J].
Abu-Ghosh, A ;
Goldman, S ;
Slone, V ;
van de Ven, C ;
Suen, Y ;
Murphy, L ;
Sender, L ;
Cairo, MS .
BONE MARROW TRANSPLANTATION, 1999, 24 (05) :535-544
[2]   A direct estimate of the human αβ T cell receptor diversity [J].
Arstila, TP ;
Casrouge, A ;
Baron, V ;
Even, J ;
Kanellopoulos, J ;
Kourilsky, P .
SCIENCE, 1999, 286 (5441) :958-961
[3]   Characterization of dendritic cell differentiation pathways from cord blood CD34+CD7+CD45RA+ hematopoietic progenitor cells [J].
Canque, B ;
Camus, S ;
Dalloul, A ;
Kahn, E ;
Yagello, M ;
Dezutter-Dambuyant, C ;
Schmitt, D ;
Schmitt, C ;
Gluckman, JC .
BLOOD, 2000, 96 (12) :3748-3756
[4]   Characterization of T cell repertoire in patients with graft-versus-leukemia after donor lymphocyte infusion [J].
Claret, EJ ;
Alyea, EP ;
Orsini, E ;
Pickett, CC ;
Collins, H ;
Wang, YL ;
Neuberg, D ;
Soiffer, RJ ;
Ritz, J .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (04) :855-866
[5]   Human cord blood progenitors sustain thymic T-cell development and a novel form of angiogenesis [J].
Crisa, L ;
Cirulli, V ;
Smith, KA ;
Ellisman, MH ;
Torbett, BE ;
Salomon, DR .
BLOOD, 1999, 94 (11) :3928-3940
[6]   Changes in thymic function with age and during the treatment of HIV infection [J].
Douek, DC ;
McFarland, RD ;
Keiser, PH ;
Gage, EA ;
Massey, JM ;
Haynes, BF ;
Polis, MA ;
Haase, AT ;
Feinberg, MB ;
Sullivan, JL ;
Jamieson, BD ;
Zack, JA ;
Picker, LJ ;
Koup, RA .
NATURE, 1998, 396 (6712) :690-695
[7]   Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution [J].
Douek, DC ;
Vescio, RA ;
Betts, MR ;
Brenchley, JM ;
Hill, BJ ;
Zhang, L ;
Berenson, JR ;
Collins, RH ;
Koup, RA .
LANCET, 2000, 355 (9218) :1875-1881
[8]   Reconstitution of the T-cell compartment after bone marrow transplantation: Restoration of the repertoire by thymic emigrants [J].
Dumont-Girard, F ;
Roux, E ;
van Lier, RA ;
Hale, G ;
Helg, C ;
Chapuis, B ;
Starobinski, M ;
Roosnek, E .
BLOOD, 1998, 92 (11) :4464-4471
[9]   Memory T cells constitute a subset of the human CD8+CD45RA+ pool with distinct phenotypic and migratory characteristics [J].
Faint, JM ;
Annels, NE ;
Curnow, SJ ;
Shields, P ;
Pilling, D ;
Hislop, AD ;
Wu, LJ ;
Akbar, AN ;
Buckley, CD ;
Moss, PAH ;
Adams, DH ;
Rickinson, AB ;
Salmon, M .
JOURNAL OF IMMUNOLOGY, 2001, 167 (01) :212-220
[10]  
FALLEN P, 2000, CORD BLOOD CHARACTER, P39