Late diversification in the clonal composition of human cytomegalovirus-specific CD8+ T cells following allogeneic hemopoietic stem cell transplantation

被引:48
作者
Gandhi, MK
Wills, MR
Okecha, G
Day, EK
Hicks, R
Marcus, RE
Sissons, JGP
Carmichael, AJ
机构
[1] Univ Cambridge, Sch Clin, Dept Med, Cambridge CB2 2QQ, England
[2] Univ Cambridge, Sch Clin, Dept Haematol, Cambridge, England
关键词
D O I
10.1182/blood-2002-12-3689
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To investigate the mechanisms of human T-cell reconstitution following allogeneic hemopoietic stem cell transplantation (alloSCT), we analyzed the clonal composition of human cytomegalovirus (HCMV)specific or Epstein-Barr virus (EBV)specific CD8(+) T cells in 10 alloSC transplant recipients and their donors. All virus-specific CD8+ T-cell clones isolated from recipients after alloSCT contained DNA of donor origin. In all 6 D+/R+ sibling alloSCTs from seropositive donors into seropositive recipients, donor virus-specific clones transferred in the allograft underwent early expansion and were maintained long term in the recipient. In contrast, in 2 of 3 HCMV D+/R- alloSC transplant recipients in whom there was no detectable HCMV infection, donor HCMV-specific clones were undetectable, whereas donor EBV-specific clones were maintained in the same EBV-seropositive recipients, suggesting that transferred clones require antigen for their maintenance. Following D-/R+ transplantation from 3 seronegative donors into seropositive recipients, a delayed primary virus-specific CD8+ T-cell response was observed, in which the T cells contained donor DNA, suggesting that new antigen-specific T cells arose in the recipient from donor-derived progenitors. In 2 of 4 HCMV D+/R+ sibling allograft recipients the clonal composition underwent diversification as compared with their donors, with delayed persistent expansion of HCMV-specific clones that were undetectable in the donor or in the recipient during the early months after transplantation; this diversification may represent expansion of new clones generated from donor-derived progenitors. We conclude that, following alloSCT, late diversification of the HCMV-specific CD8+ T-cell clonal repertoire can occur in response to persistent viral antigen. (C) 2003 by The American Society of Hematology.
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页码:3427 / 3438
页数:12
相关论文
共 35 条
[1]   Cytomegalovirus-specific cellular immune responses and viremia in recipients of allogeneic stem cell transplants [J].
Aubert, G ;
Hassan-Walker, AF ;
Madrigal, JA ;
Emery, VC ;
Morte, C ;
Grace, S ;
Koh, MBC ;
Potter, M ;
Prentice, HG ;
Dodi, IA ;
Travers, PJ .
JOURNAL OF INFECTIOUS DISEASES, 2001, 184 (08) :955-963
[2]   Effect of the MTHFRC677T variant on risk of venous thromboembolism:: Interaction with factor V Leiden and prothrombin (F2G20210A) mutations [J].
Brown, K ;
Luddington, R ;
Baglin, T .
BRITISH JOURNAL OF HAEMATOLOGY, 1998, 103 (01) :42-44
[3]  
BUEL E, 1995, J FORENSIC SCI, V40, P641
[4]  
BUTTURINI A, 1986, BLOOD, V68, P954
[5]   HPA genotyping by PCR sequence-specific priming (PCR-SSP): A streamlined method for rapid routine investigations [J].
Cavanagh, G ;
Dunn, AN ;
Chapman, CE ;
Metcalfe, P .
TRANSFUSION MEDICINE, 1997, 7 (01) :41-45
[6]   Direct visualization of cytomegalovirus-specific T-cell reconstitution after allogeneic stem cell transplantation [J].
Cwynarski, K ;
Ainsworth, J ;
Cobbold, M ;
Wagner, S ;
Mahendra, P ;
Apperley, J ;
Goldman, J ;
Craddock, C ;
Moss, PAH .
BLOOD, 2001, 97 (05) :1232-1240
[7]   Differentiation of cytomegalovirus-specific CD8+ T cells in healthy and immunosuppressed virus carriers [J].
Gamadia, LE ;
Rentenaar, RJ ;
Baars, PA ;
Remmerswaal, EBM ;
Surachno, S ;
Weel, JFL ;
Toebes, M ;
Schumacher, TNM ;
ten Berge, IJM ;
van Lier, RAW .
BLOOD, 2001, 98 (03) :754-761
[8]   Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8+ T lymphocytes in healthy seropositive donors [J].
Gillespie, GMA ;
Wills, MR ;
Appay, V ;
O'Callaghan, C ;
Murphy, M ;
Smith, N ;
Sissons, P ;
Rowland-Jones, S ;
Bell, JI ;
Moss, PAH .
JOURNAL OF VIROLOGY, 2000, 74 (17) :8140-8150
[9]   STRATEGIES FOR THE PREVENTION OF CYTOMEGALOVIRUS DISEASE AFTER MARROW TRANSPLANTATION [J].
GOODRICH, JM ;
BOECKH, M ;
BOWDEN, R .
CLINICAL INFECTIOUS DISEASES, 1994, 19 (02) :287-298
[10]   Tetramer-based quantification of cytomegalovirus (CMV)-specific CD8+ T lymphocytes in T-cell-depleted stem cell grafts and after transplantation may identify patients at risk for progressive CMV infection [J].
Gratama, JW ;
van Esser, JWJ ;
Lamers, CHJ ;
Toumay, C ;
Löwenberg, B ;
Bolhuis, RLH ;
Cornelissen, JJ .
BLOOD, 2001, 98 (05) :1358-1364