Reconstitution of T-cell repertoire after autologous stem cell transplantation: influence of CD34 selection and cytomegalovirus infection

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Reconstitution of T-cell repertoire after autologous stem cell transplantation : influence of CD34 selection and cytomegalovirus infection. / Peggs, Karl S; Verfuerth, Stephanie; Pizzey, Arnold; Khan, Naeem; Moss, Paul; Goldstone, Anthony H; Yong, Kwee; Mackinnon, Stephen.

In: Biology of Blood and Marrow Transplantation, Vol. 9, No. 3, 01.03.2003, p. 198-205.

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Peggs, Karl S ; Verfuerth, Stephanie ; Pizzey, Arnold ; Khan, Naeem ; Moss, Paul ; Goldstone, Anthony H ; Yong, Kwee ; Mackinnon, Stephen. / Reconstitution of T-cell repertoire after autologous stem cell transplantation : influence of CD34 selection and cytomegalovirus infection. In: Biology of Blood and Marrow Transplantation. 2003 ; Vol. 9, No. 3. pp. 198-205.

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@article{8e4cc19f48284f9bbaab934b5c9f4e34,
title = "Reconstitution of T-cell repertoire after autologous stem cell transplantation: influence of CD34 selection and cytomegalovirus infection",
abstract = "The period of immunodeficiency following autologous hematopoietic stem cell transplantation is characterized by transient expansions of CD8+CD45RO+CD57+ T lymphocytes, displaying markers of an activated phenotype. Most evidence suggests that this early reconstitution results from proliferation of mature T cells that have survived conditioning or were transferred with the graft. Although homeostatic mechanisms are thought to act in maintaining total T-cell numbers, the degree to which antigen-driven expansions contribute and the nature of the stimulating antigens remain unclear. CD34 selection of stem cell grafts reduces the available T-cell pool, potentially delaying immune reconstitution and resulting in increased infective complications. In the allogeneic transplantation setting, lymphopenia has been associated with cytomegalovirus (CMV) infection risk and, if persistent, with adverse outcome. We prospectively studied patients undergoing CD34-selected (n = 13) or unselected (n = 13) autologous hematopoeitic stem cell transplantation for immune reconstitution and CMV infection. No significant differences were demonstrated between graft types with respect to lymphocyte subset recovery, T-cell receptor beta-chain variable region spectratype diversity, or CMV DNA detection rates (45% versus 40%). CMV infection was associated with a trend toward higher rather than lower CD8+ counts at 6 weeks posttransplantation (P =.08) that became significant by 3 months (P=.007), and that was associated with decreased T-cell receptor beta-chain variable region spectratype diversity (P =.01). CMV-specific HLA-tetramer analysis demonstrated transient expansions with CDR3 lengths corresponding to those of some of the major posttransplantation T-cell expansions demonstrated by spectratype analysis suggesting that CMV-specific T cells contribute to the pattern of immune reconstitution.",
author = "Peggs, {Karl S} and Stephanie Verfuerth and Arnold Pizzey and Naeem Khan and Paul Moss and Goldstone, {Anthony H} and Kwee Yong and Stephen Mackinnon",
note = "Copyright 2003 American Society for Blood and Marrow Transplantation",
year = "2003",
month = mar,
day = "1",
doi = "10.1016/S1083-8791(03)70010-X",
language = "English",
volume = "9",
pages = "198--205",
journal = "Biology of Blood and Marrow Transplantation ",
issn = "1083-8791",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - Reconstitution of T-cell repertoire after autologous stem cell transplantation

T2 - influence of CD34 selection and cytomegalovirus infection

AU - Peggs, Karl S

AU - Verfuerth, Stephanie

AU - Pizzey, Arnold

AU - Khan, Naeem

AU - Moss, Paul

AU - Goldstone, Anthony H

AU - Yong, Kwee

AU - Mackinnon, Stephen

N1 - Copyright 2003 American Society for Blood and Marrow Transplantation

PY - 2003/3/1

Y1 - 2003/3/1

N2 - The period of immunodeficiency following autologous hematopoietic stem cell transplantation is characterized by transient expansions of CD8+CD45RO+CD57+ T lymphocytes, displaying markers of an activated phenotype. Most evidence suggests that this early reconstitution results from proliferation of mature T cells that have survived conditioning or were transferred with the graft. Although homeostatic mechanisms are thought to act in maintaining total T-cell numbers, the degree to which antigen-driven expansions contribute and the nature of the stimulating antigens remain unclear. CD34 selection of stem cell grafts reduces the available T-cell pool, potentially delaying immune reconstitution and resulting in increased infective complications. In the allogeneic transplantation setting, lymphopenia has been associated with cytomegalovirus (CMV) infection risk and, if persistent, with adverse outcome. We prospectively studied patients undergoing CD34-selected (n = 13) or unselected (n = 13) autologous hematopoeitic stem cell transplantation for immune reconstitution and CMV infection. No significant differences were demonstrated between graft types with respect to lymphocyte subset recovery, T-cell receptor beta-chain variable region spectratype diversity, or CMV DNA detection rates (45% versus 40%). CMV infection was associated with a trend toward higher rather than lower CD8+ counts at 6 weeks posttransplantation (P =.08) that became significant by 3 months (P=.007), and that was associated with decreased T-cell receptor beta-chain variable region spectratype diversity (P =.01). CMV-specific HLA-tetramer analysis demonstrated transient expansions with CDR3 lengths corresponding to those of some of the major posttransplantation T-cell expansions demonstrated by spectratype analysis suggesting that CMV-specific T cells contribute to the pattern of immune reconstitution.

AB - The period of immunodeficiency following autologous hematopoietic stem cell transplantation is characterized by transient expansions of CD8+CD45RO+CD57+ T lymphocytes, displaying markers of an activated phenotype. Most evidence suggests that this early reconstitution results from proliferation of mature T cells that have survived conditioning or were transferred with the graft. Although homeostatic mechanisms are thought to act in maintaining total T-cell numbers, the degree to which antigen-driven expansions contribute and the nature of the stimulating antigens remain unclear. CD34 selection of stem cell grafts reduces the available T-cell pool, potentially delaying immune reconstitution and resulting in increased infective complications. In the allogeneic transplantation setting, lymphopenia has been associated with cytomegalovirus (CMV) infection risk and, if persistent, with adverse outcome. We prospectively studied patients undergoing CD34-selected (n = 13) or unselected (n = 13) autologous hematopoeitic stem cell transplantation for immune reconstitution and CMV infection. No significant differences were demonstrated between graft types with respect to lymphocyte subset recovery, T-cell receptor beta-chain variable region spectratype diversity, or CMV DNA detection rates (45% versus 40%). CMV infection was associated with a trend toward higher rather than lower CD8+ counts at 6 weeks posttransplantation (P =.08) that became significant by 3 months (P=.007), and that was associated with decreased T-cell receptor beta-chain variable region spectratype diversity (P =.01). CMV-specific HLA-tetramer analysis demonstrated transient expansions with CDR3 lengths corresponding to those of some of the major posttransplantation T-cell expansions demonstrated by spectratype analysis suggesting that CMV-specific T cells contribute to the pattern of immune reconstitution.

UR - http://www.scopus.com/inward/record.url?scp=0642308424&partnerID=8YFLogxK

U2 - 10.1016/S1083-8791(03)70010-X

DO - 10.1016/S1083-8791(03)70010-X

M3 - Article

C2 - 12652471

VL - 9

SP - 198

EP - 205

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 3

ER -