Deficiency of cytomegalovirus (CMV)-specific CD8+ T cells in patients presenting with late-onset CMV disease several years after transplantation

Nathan W Cummins, P. J. Deziel, R. S. Abraham, Raymund R Razonable

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42 Citations (Scopus)

Abstract

Cytomegalovirus (CMV) is a major cause of morbidity and mortality among transplant recipients. The routine use of anti-CMV prophylaxis has modified the epidemiology of post-transplant CMV infection by delaying the onset of clinical disease. While the majority of delayed-onset CMV disease still occurs during the first year after transplant, reports of late-onset CMV disease presenting many years after transplantation are increasing. Here, we describe 2 CMV-seropositive transplant recipients who presented with late-onset CMV disease at 8 and 11 years after transplantation. To determine whether CMV disease occurring at a very late period after transplantation is related to immune competence, we assessed global and CMV-specific cellular immunity by evaluating the activation capability of CD8+ T cells to a mitogenic stimulus and by quantitative and functional analysis (as assessed by intracellular cytokine production and degranulation) of CMV-specific CD8+ T cells. In both patients, we demonstrated the absence or marked deficiency of CMV-specific T-cell immunity despite CMV seropositivity, and in one patient, a partial defect in the immune response to phorbol myristate acetate and ionomycin suggesting impaired global immune competence. Hence, our data suggest that late-onset CMV disease occurring many years after transplantation remains related to defects in the immune competence of patients. Measurement of CMV-specific cellular immune competence may therefore provide an additional tool to screen for patients at high risk of developing late-onset CMV disease. The clinical utility of this assay, however, will need to be evaluated in larger prospective studies.

Original languageEnglish (US)
Pages (from-to)20-27
Number of pages8
JournalTransplant Infectious Disease
Volume11
Issue number1
DOIs
StatePublished - Feb 2009

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Cytomegalovirus
Transplantation
T-Lymphocytes
Mental Competency
Late Onset Disorders
Transplants
Ionomycin
Cytomegalovirus Infections
Tetradecanoylphorbol Acetate
Cellular Immunity
Immunity
Epidemiology
Prospective Studies

Keywords

  • CD8+
  • Cytomegalovirus
  • Immunity
  • Kidney transplantation
  • Late onset
  • Outcome
  • T cells

ASJC Scopus subject areas

  • Transplantation
  • Infectious Diseases

Cite this

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abstract = "Cytomegalovirus (CMV) is a major cause of morbidity and mortality among transplant recipients. The routine use of anti-CMV prophylaxis has modified the epidemiology of post-transplant CMV infection by delaying the onset of clinical disease. While the majority of delayed-onset CMV disease still occurs during the first year after transplant, reports of late-onset CMV disease presenting many years after transplantation are increasing. Here, we describe 2 CMV-seropositive transplant recipients who presented with late-onset CMV disease at 8 and 11 years after transplantation. To determine whether CMV disease occurring at a very late period after transplantation is related to immune competence, we assessed global and CMV-specific cellular immunity by evaluating the activation capability of CD8+ T cells to a mitogenic stimulus and by quantitative and functional analysis (as assessed by intracellular cytokine production and degranulation) of CMV-specific CD8+ T cells. In both patients, we demonstrated the absence or marked deficiency of CMV-specific T-cell immunity despite CMV seropositivity, and in one patient, a partial defect in the immune response to phorbol myristate acetate and ionomycin suggesting impaired global immune competence. Hence, our data suggest that late-onset CMV disease occurring many years after transplantation remains related to defects in the immune competence of patients. Measurement of CMV-specific cellular immune competence may therefore provide an additional tool to screen for patients at high risk of developing late-onset CMV disease. The clinical utility of this assay, however, will need to be evaluated in larger prospective studies.",
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AU - Deziel, P. J.

AU - Abraham, R. S.

AU - Razonable, Raymund R

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N2 - Cytomegalovirus (CMV) is a major cause of morbidity and mortality among transplant recipients. The routine use of anti-CMV prophylaxis has modified the epidemiology of post-transplant CMV infection by delaying the onset of clinical disease. While the majority of delayed-onset CMV disease still occurs during the first year after transplant, reports of late-onset CMV disease presenting many years after transplantation are increasing. Here, we describe 2 CMV-seropositive transplant recipients who presented with late-onset CMV disease at 8 and 11 years after transplantation. To determine whether CMV disease occurring at a very late period after transplantation is related to immune competence, we assessed global and CMV-specific cellular immunity by evaluating the activation capability of CD8+ T cells to a mitogenic stimulus and by quantitative and functional analysis (as assessed by intracellular cytokine production and degranulation) of CMV-specific CD8+ T cells. In both patients, we demonstrated the absence or marked deficiency of CMV-specific T-cell immunity despite CMV seropositivity, and in one patient, a partial defect in the immune response to phorbol myristate acetate and ionomycin suggesting impaired global immune competence. Hence, our data suggest that late-onset CMV disease occurring many years after transplantation remains related to defects in the immune competence of patients. Measurement of CMV-specific cellular immune competence may therefore provide an additional tool to screen for patients at high risk of developing late-onset CMV disease. The clinical utility of this assay, however, will need to be evaluated in larger prospective studies.

AB - Cytomegalovirus (CMV) is a major cause of morbidity and mortality among transplant recipients. The routine use of anti-CMV prophylaxis has modified the epidemiology of post-transplant CMV infection by delaying the onset of clinical disease. While the majority of delayed-onset CMV disease still occurs during the first year after transplant, reports of late-onset CMV disease presenting many years after transplantation are increasing. Here, we describe 2 CMV-seropositive transplant recipients who presented with late-onset CMV disease at 8 and 11 years after transplantation. To determine whether CMV disease occurring at a very late period after transplantation is related to immune competence, we assessed global and CMV-specific cellular immunity by evaluating the activation capability of CD8+ T cells to a mitogenic stimulus and by quantitative and functional analysis (as assessed by intracellular cytokine production and degranulation) of CMV-specific CD8+ T cells. In both patients, we demonstrated the absence or marked deficiency of CMV-specific T-cell immunity despite CMV seropositivity, and in one patient, a partial defect in the immune response to phorbol myristate acetate and ionomycin suggesting impaired global immune competence. Hence, our data suggest that late-onset CMV disease occurring many years after transplantation remains related to defects in the immune competence of patients. Measurement of CMV-specific cellular immune competence may therefore provide an additional tool to screen for patients at high risk of developing late-onset CMV disease. The clinical utility of this assay, however, will need to be evaluated in larger prospective studies.

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