Reconstitution of cytomegalovirus-specific T-cell response in allogeneic hematopoietic stem cell recipients: the contribution of six frequently recognized, virus-encoded ORFs

Transpl Infect Dis. 2016 Jun;18(3):381-9. doi: 10.1111/tid.12540. Epub 2016 Jun 9.

Abstract

Background: The reactivation of human cytomegalovirus (HCMV) in immunosuppressed patients is associated with significant morbidity. Testing HCMV-specific T-cell responses can help determine which patients are at high risk of HCMV disease. We optimized selection of HCMV antigens for detection of T-cell response of patients after allogeneic hematopoietic stem cell transplantation (HSCT) with the aim of identifying patients with insufficient control of HCMV reactivation.

Methods: T-cell immune response to HCMV was monitored in 30 patients during the first year after HSCT. The HSCT recipients were classified according to their anti-HCMV T-cell response and the presence of HCMV DNA in the blood.

Results: We observed an inverse relationship between the magnitude of HCMV-specific T-cell responses against CMV lysate, phosphoprotein (pp) 65, immediate early-1 (IE-1), UL36, and UL55, but not to US3 and US29 detected by interferon-gamma (IFNγ)- ELISPOT and the level of HCMV DNA in the blood of patients during the 30 days following sampling. The study has revealed that patients who received a graft from a seronegative donor have a lower T-cell response against HCMV and increased probability of HCMV reactivation in comparison to the patients who had received their graft from a seropositive donor.

Conclusion: The individual peptide pools and native HCMV antigens were useful for monitoring the time course of the anti-HCMV response by IFNγ-ELISPOT, which proved to have a prognostic value. Besides widely employed peptide pools of pp65 and IE-1, the use of antigens UL36 and UL55, but not US3 or US29, increased sensitivity of the test.

Keywords: ELISPOT; T cell; allogeneic stem cell transplantation; human cytomegalovirus; interferon-gamma.

MeSH terms

  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Antiviral Agents / therapeutic use
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • Enzyme-Linked Immunospot Assay
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunocompromised Host
  • Interferon-gamma / blood
  • Male
  • Middle Aged
  • Phosphoproteins / immunology
  • Viral Proteins / genetics
  • Viral Proteins / immunology*

Substances

  • Antigens, Viral
  • Antiviral Agents
  • Phosphoproteins
  • Viral Proteins
  • Interferon-gamma