Reconstitution of Human Cytomegalovirus-Specific CD4+ T Cells is Critical for Control of Virus Reactivation in Hematopoietic Stem Cell Transplant Recipients but Does Not Prevent Organ Infection

Elisa Gabanti, Daniele Lilleri, Francesco Ripamonti, Francesca Bruno, Paola Zelini, Milena Furione, Anna A. Colombo, Emilio P. Alessandrino, Giuseppe Gerna

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Abstract

The relative contribution of human cytomegalovirus (HMCV)-specific CD4+ and CD8+ T cells to the control of HCMV infection in hematopoietic stem cell transplant (HSCT) recipients is still controversial. HCMV reactivation and HCMV-specific CD4+ and CD8+ T cell reconstitution were monitored for 1 year in 63 HCMV-seropositive patients receiving HSCT. HCMV reactivation was detected in all but 2 patients. In 20 of 63 (31.7%) patients (group 1) HCMV infection resolved spontaneously, whereas 32 of 63 (50.8%) patients (group 2) controlled the infection after a single short-course of pre-emptive therapy and the remaining 9 (14.3%) patients (group 3) suffered from relapsing episodes of HCMV infection, requiring multiple courses of antiviral therapy. The kinetics and magnitude of HCMV-specific CD8+ T cell reconstitution were comparable among the 3 groups, but HCMV-specific CD4+ T cells were lower in number in patients requiring antiviral treatment. HCMV-seronegative donors, as well as unrelated donors (receiving antithymocyte globulin) and acute graft-versus-host disease (GVHD) were associated with both delayed HCMV-specific CD4+ T cell reconstitution and severity of infection. Conversely, these risk factors had no impact on HCMV-specific CD8+ T cells. Eight patients with previous GVHD suffered from HCMV gastrointestinal disease, although in the presence of HCMV-specific CD4+ and CD8+ systemic immunity and undetectable HCMV DNA in blood. Reconstitution of systemic HCMV-specific CD4+ T cell immunity is required for control of HCMV reactivation in adult HSCT recipients, but it may not be sufficient to prevent late-onset organ localization in patients with GVHD. HCMV-specific CD8+ T cells contribute to control of HCMV infection, but only after HCMV-specific CD4+ T cell reconstitution.

Original languageEnglish
Pages (from-to)2192-2202
Number of pages11
JournalBiology of Blood and Marrow Transplantation
Volume21
Issue number12
DOIs
Publication statusPublished - Dec 1 2015

Fingerprint

Hematopoietic Stem Cells
Cytomegalovirus
Viruses
T-Lymphocytes
Transplants
Infection
Graft vs Host Disease
Infection Control
Antiviral Agents
Immunity
Transplant Recipients
Unrelated Donors
Adult Stem Cells
Antilymphocyte Serum
Gastrointestinal Diseases
Therapeutics
Tissue Donors
DNA

Keywords

  • CD4 T cells
  • CD8 T cells
  • Gastrointestinal disease
  • Hematopoietic stem cell transplantation
  • Human cytomegalovirus
  • Specific T cell immunity

ASJC Scopus subject areas

  • Transplantation
  • Hematology

Cite this

@article{caf2f139fac247339ec862b642ace97c,
title = "Reconstitution of Human Cytomegalovirus-Specific CD4+ T Cells is Critical for Control of Virus Reactivation in Hematopoietic Stem Cell Transplant Recipients but Does Not Prevent Organ Infection",
abstract = "The relative contribution of human cytomegalovirus (HMCV)-specific CD4+ and CD8+ T cells to the control of HCMV infection in hematopoietic stem cell transplant (HSCT) recipients is still controversial. HCMV reactivation and HCMV-specific CD4+ and CD8+ T cell reconstitution were monitored for 1 year in 63 HCMV-seropositive patients receiving HSCT. HCMV reactivation was detected in all but 2 patients. In 20 of 63 (31.7{\%}) patients (group 1) HCMV infection resolved spontaneously, whereas 32 of 63 (50.8{\%}) patients (group 2) controlled the infection after a single short-course of pre-emptive therapy and the remaining 9 (14.3{\%}) patients (group 3) suffered from relapsing episodes of HCMV infection, requiring multiple courses of antiviral therapy. The kinetics and magnitude of HCMV-specific CD8+ T cell reconstitution were comparable among the 3 groups, but HCMV-specific CD4+ T cells were lower in number in patients requiring antiviral treatment. HCMV-seronegative donors, as well as unrelated donors (receiving antithymocyte globulin) and acute graft-versus-host disease (GVHD) were associated with both delayed HCMV-specific CD4+ T cell reconstitution and severity of infection. Conversely, these risk factors had no impact on HCMV-specific CD8+ T cells. Eight patients with previous GVHD suffered from HCMV gastrointestinal disease, although in the presence of HCMV-specific CD4+ and CD8+ systemic immunity and undetectable HCMV DNA in blood. Reconstitution of systemic HCMV-specific CD4+ T cell immunity is required for control of HCMV reactivation in adult HSCT recipients, but it may not be sufficient to prevent late-onset organ localization in patients with GVHD. HCMV-specific CD8+ T cells contribute to control of HCMV infection, but only after HCMV-specific CD4+ T cell reconstitution.",
keywords = "CD4 T cells, CD8 T cells, Gastrointestinal disease, Hematopoietic stem cell transplantation, Human cytomegalovirus, Specific T cell immunity",
author = "Elisa Gabanti and Daniele Lilleri and Francesco Ripamonti and Francesca Bruno and Paola Zelini and Milena Furione and Colombo, {Anna A.} and Alessandrino, {Emilio P.} and Giuseppe Gerna",
year = "2015",
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journal = "Biology of Blood and Marrow Transplantation",
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AU - Gabanti, Elisa

AU - Lilleri, Daniele

AU - Ripamonti, Francesco

AU - Bruno, Francesca

AU - Zelini, Paola

AU - Furione, Milena

AU - Colombo, Anna A.

AU - Alessandrino, Emilio P.

AU - Gerna, Giuseppe

PY - 2015/12/1

Y1 - 2015/12/1

N2 - The relative contribution of human cytomegalovirus (HMCV)-specific CD4+ and CD8+ T cells to the control of HCMV infection in hematopoietic stem cell transplant (HSCT) recipients is still controversial. HCMV reactivation and HCMV-specific CD4+ and CD8+ T cell reconstitution were monitored for 1 year in 63 HCMV-seropositive patients receiving HSCT. HCMV reactivation was detected in all but 2 patients. In 20 of 63 (31.7%) patients (group 1) HCMV infection resolved spontaneously, whereas 32 of 63 (50.8%) patients (group 2) controlled the infection after a single short-course of pre-emptive therapy and the remaining 9 (14.3%) patients (group 3) suffered from relapsing episodes of HCMV infection, requiring multiple courses of antiviral therapy. The kinetics and magnitude of HCMV-specific CD8+ T cell reconstitution were comparable among the 3 groups, but HCMV-specific CD4+ T cells were lower in number in patients requiring antiviral treatment. HCMV-seronegative donors, as well as unrelated donors (receiving antithymocyte globulin) and acute graft-versus-host disease (GVHD) were associated with both delayed HCMV-specific CD4+ T cell reconstitution and severity of infection. Conversely, these risk factors had no impact on HCMV-specific CD8+ T cells. Eight patients with previous GVHD suffered from HCMV gastrointestinal disease, although in the presence of HCMV-specific CD4+ and CD8+ systemic immunity and undetectable HCMV DNA in blood. Reconstitution of systemic HCMV-specific CD4+ T cell immunity is required for control of HCMV reactivation in adult HSCT recipients, but it may not be sufficient to prevent late-onset organ localization in patients with GVHD. HCMV-specific CD8+ T cells contribute to control of HCMV infection, but only after HCMV-specific CD4+ T cell reconstitution.

AB - The relative contribution of human cytomegalovirus (HMCV)-specific CD4+ and CD8+ T cells to the control of HCMV infection in hematopoietic stem cell transplant (HSCT) recipients is still controversial. HCMV reactivation and HCMV-specific CD4+ and CD8+ T cell reconstitution were monitored for 1 year in 63 HCMV-seropositive patients receiving HSCT. HCMV reactivation was detected in all but 2 patients. In 20 of 63 (31.7%) patients (group 1) HCMV infection resolved spontaneously, whereas 32 of 63 (50.8%) patients (group 2) controlled the infection after a single short-course of pre-emptive therapy and the remaining 9 (14.3%) patients (group 3) suffered from relapsing episodes of HCMV infection, requiring multiple courses of antiviral therapy. The kinetics and magnitude of HCMV-specific CD8+ T cell reconstitution were comparable among the 3 groups, but HCMV-specific CD4+ T cells were lower in number in patients requiring antiviral treatment. HCMV-seronegative donors, as well as unrelated donors (receiving antithymocyte globulin) and acute graft-versus-host disease (GVHD) were associated with both delayed HCMV-specific CD4+ T cell reconstitution and severity of infection. Conversely, these risk factors had no impact on HCMV-specific CD8+ T cells. Eight patients with previous GVHD suffered from HCMV gastrointestinal disease, although in the presence of HCMV-specific CD4+ and CD8+ systemic immunity and undetectable HCMV DNA in blood. Reconstitution of systemic HCMV-specific CD4+ T cell immunity is required for control of HCMV reactivation in adult HSCT recipients, but it may not be sufficient to prevent late-onset organ localization in patients with GVHD. HCMV-specific CD8+ T cells contribute to control of HCMV infection, but only after HCMV-specific CD4+ T cell reconstitution.

KW - CD4 T cells

KW - CD8 T cells

KW - Gastrointestinal disease

KW - Hematopoietic stem cell transplantation

KW - Human cytomegalovirus

KW - Specific T cell immunity

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