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

Biol Blood Marrow Transplant. 2015 Dec;21(12):2192-2202. doi: 10.1016/j.bbmt.2015.08.002. Epub 2015 Aug 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Antiviral Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / virology
  • Cell Proliferation
  • Chronic Disease
  • Cytomegalovirus / immunology
  • Cytomegalovirus / pathogenicity
  • Cytomegalovirus Infections / drug therapy*
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / mortality
  • Cytomegalovirus Infections / pathology
  • Female
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology
  • Hematologic Neoplasms / drug therapy*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / pathology
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Survival Analysis
  • Transplantation, Homologous
  • Treatment Outcome
  • Virus Activation

Substances

  • Antineoplastic Agents
  • Antiviral Agents