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

Research output: Contribution to journalArticle

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

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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

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