Kinetics of interferon-gamma producing cytomegalovirus (CMV)-specific CD4+ and CD8+ T lymphocytes and the risk of subsequent CMV viremia after allogeneic hematopoietic stem cell transplantation

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Abstract

Deficiencies in cytomegalovirus (CMV)-specific T lymphocytes impair the immunologic response against CMV reactivation after allogeneic hematopoietic stem cell transplantation (HSCT). Methods. A time-dependent analysis was conducted to determine the association between the percentages and kinetics of interferon-gamma-producing CMV-specific CD4+ and CD8+ T lymphocytes and CMV viremia among 30 allogeneic HSCT recipients. Results. Higher percentages of CD4+ T lymphocytes activated with CMVpp65 (hazard ratio [HR]: 2.06; 95% confidence interval [95% CI]: 1.18-3.6; P=0.011) and CMV lysate (HR: 1.18; 95% CI: 0.99-1.42; P=0.072), and higher percentages of CD8+ T lymphocytes activated by CMV immediate early-1 (HR: 1.2; 95% CI: 1.01-1.43; P=0.038) and CMVpp65 (HR: 1.12; 95% CI: 1.0-1.27; P=0.060) were associated with time-to-CMV viremia. Furthermore, a higher degree in the decline of CMV lysate-activated CD4+ T lymphocytes (HR: 1.14; 95% CI: 0.96-1.36; P=0.125) and CMVpp65-activated CD8+ T lymphocytes (HR: 1.36; 95% CI: 1.03-1.78; P=0.031) was suggestive of or significantly associated with time-to-CMV viremia. Conclusions. Higher levels of CMV-specific CD4+ and CD8+ T lymphocytes were associated with subsequent CMV viremia after HSCT. The association between CMV viremia and the degree of decline in CMV-specific T lymphocytes suggests that severe disruption in homeostatic CMV-specific immune environment contributes to the immunopathogenesis of CMV after allogeneic HSCT.

Original languageEnglish (US)
Pages (from-to)519-528
Number of pages10
JournalTransplant Infectious Disease
Volume11
Issue number6
DOIs
StatePublished - Dec 2009

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Viremia
Hematopoietic Stem Cell Transplantation
Cytomegalovirus
Interferon-gamma
T-Lymphocytes
Confidence Intervals

Keywords

  • Bacterial infection
  • CMV peptide
  • Cytokine flow cytometry
  • Immune reconstitution
  • Immunity
  • Interferon-gamma

ASJC Scopus subject areas

  • Transplantation
  • Infectious Diseases

Cite this

@article{a9ada7c7939841c88f4ebfab8b7d3765,
title = "Kinetics of interferon-gamma producing cytomegalovirus (CMV)-specific CD4+ and CD8+ T lymphocytes and the risk of subsequent CMV viremia after allogeneic hematopoietic stem cell transplantation",
abstract = "Deficiencies in cytomegalovirus (CMV)-specific T lymphocytes impair the immunologic response against CMV reactivation after allogeneic hematopoietic stem cell transplantation (HSCT). Methods. A time-dependent analysis was conducted to determine the association between the percentages and kinetics of interferon-gamma-producing CMV-specific CD4+ and CD8+ T lymphocytes and CMV viremia among 30 allogeneic HSCT recipients. Results. Higher percentages of CD4+ T lymphocytes activated with CMVpp65 (hazard ratio [HR]: 2.06; 95{\%} confidence interval [95{\%} CI]: 1.18-3.6; P=0.011) and CMV lysate (HR: 1.18; 95{\%} CI: 0.99-1.42; P=0.072), and higher percentages of CD8+ T lymphocytes activated by CMV immediate early-1 (HR: 1.2; 95{\%} CI: 1.01-1.43; P=0.038) and CMVpp65 (HR: 1.12; 95{\%} CI: 1.0-1.27; P=0.060) were associated with time-to-CMV viremia. Furthermore, a higher degree in the decline of CMV lysate-activated CD4+ T lymphocytes (HR: 1.14; 95{\%} CI: 0.96-1.36; P=0.125) and CMVpp65-activated CD8+ T lymphocytes (HR: 1.36; 95{\%} CI: 1.03-1.78; P=0.031) was suggestive of or significantly associated with time-to-CMV viremia. Conclusions. Higher levels of CMV-specific CD4+ and CD8+ T lymphocytes were associated with subsequent CMV viremia after HSCT. The association between CMV viremia and the degree of decline in CMV-specific T lymphocytes suggests that severe disruption in homeostatic CMV-specific immune environment contributes to the immunopathogenesis of CMV after allogeneic HSCT.",
keywords = "Bacterial infection, CMV peptide, Cytokine flow cytometry, Immune reconstitution, Immunity, Interferon-gamma",
author = "Eid, {A. J.} and Brown, {R. A.} and William Hogan and Lahr, {B. D.} and Eckel-Passow, {Jeanette E} and Litzow, {Mark R} and Razonable, {Raymund R}",
year = "2009",
month = "12",
doi = "10.1111/j.1399-3062.2009.00446.x",
language = "English (US)",
volume = "11",
pages = "519--528",
journal = "Transplant Infectious Disease",
issn = "1398-2273",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Kinetics of interferon-gamma producing cytomegalovirus (CMV)-specific CD4+ and CD8+ T lymphocytes and the risk of subsequent CMV viremia after allogeneic hematopoietic stem cell transplantation

AU - Eid, A. J.

AU - Brown, R. A.

AU - Hogan, William

AU - Lahr, B. D.

AU - Eckel-Passow, Jeanette E

AU - Litzow, Mark R

AU - Razonable, Raymund R

PY - 2009/12

Y1 - 2009/12

N2 - Deficiencies in cytomegalovirus (CMV)-specific T lymphocytes impair the immunologic response against CMV reactivation after allogeneic hematopoietic stem cell transplantation (HSCT). Methods. A time-dependent analysis was conducted to determine the association between the percentages and kinetics of interferon-gamma-producing CMV-specific CD4+ and CD8+ T lymphocytes and CMV viremia among 30 allogeneic HSCT recipients. Results. Higher percentages of CD4+ T lymphocytes activated with CMVpp65 (hazard ratio [HR]: 2.06; 95% confidence interval [95% CI]: 1.18-3.6; P=0.011) and CMV lysate (HR: 1.18; 95% CI: 0.99-1.42; P=0.072), and higher percentages of CD8+ T lymphocytes activated by CMV immediate early-1 (HR: 1.2; 95% CI: 1.01-1.43; P=0.038) and CMVpp65 (HR: 1.12; 95% CI: 1.0-1.27; P=0.060) were associated with time-to-CMV viremia. Furthermore, a higher degree in the decline of CMV lysate-activated CD4+ T lymphocytes (HR: 1.14; 95% CI: 0.96-1.36; P=0.125) and CMVpp65-activated CD8+ T lymphocytes (HR: 1.36; 95% CI: 1.03-1.78; P=0.031) was suggestive of or significantly associated with time-to-CMV viremia. Conclusions. Higher levels of CMV-specific CD4+ and CD8+ T lymphocytes were associated with subsequent CMV viremia after HSCT. The association between CMV viremia and the degree of decline in CMV-specific T lymphocytes suggests that severe disruption in homeostatic CMV-specific immune environment contributes to the immunopathogenesis of CMV after allogeneic HSCT.

AB - Deficiencies in cytomegalovirus (CMV)-specific T lymphocytes impair the immunologic response against CMV reactivation after allogeneic hematopoietic stem cell transplantation (HSCT). Methods. A time-dependent analysis was conducted to determine the association between the percentages and kinetics of interferon-gamma-producing CMV-specific CD4+ and CD8+ T lymphocytes and CMV viremia among 30 allogeneic HSCT recipients. Results. Higher percentages of CD4+ T lymphocytes activated with CMVpp65 (hazard ratio [HR]: 2.06; 95% confidence interval [95% CI]: 1.18-3.6; P=0.011) and CMV lysate (HR: 1.18; 95% CI: 0.99-1.42; P=0.072), and higher percentages of CD8+ T lymphocytes activated by CMV immediate early-1 (HR: 1.2; 95% CI: 1.01-1.43; P=0.038) and CMVpp65 (HR: 1.12; 95% CI: 1.0-1.27; P=0.060) were associated with time-to-CMV viremia. Furthermore, a higher degree in the decline of CMV lysate-activated CD4+ T lymphocytes (HR: 1.14; 95% CI: 0.96-1.36; P=0.125) and CMVpp65-activated CD8+ T lymphocytes (HR: 1.36; 95% CI: 1.03-1.78; P=0.031) was suggestive of or significantly associated with time-to-CMV viremia. Conclusions. Higher levels of CMV-specific CD4+ and CD8+ T lymphocytes were associated with subsequent CMV viremia after HSCT. The association between CMV viremia and the degree of decline in CMV-specific T lymphocytes suggests that severe disruption in homeostatic CMV-specific immune environment contributes to the immunopathogenesis of CMV after allogeneic HSCT.

KW - Bacterial infection

KW - CMV peptide

KW - Cytokine flow cytometry

KW - Immune reconstitution

KW - Immunity

KW - Interferon-gamma

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U2 - 10.1111/j.1399-3062.2009.00446.x

DO - 10.1111/j.1399-3062.2009.00446.x

M3 - Article

VL - 11

SP - 519

EP - 528

JO - Transplant Infectious Disease

JF - Transplant Infectious Disease

SN - 1398-2273

IS - 6

ER -