Immune Control of Human Cytomegalovirus (HCMV) Infection in HCMV-Seropositive Solid Organ Transplant Recipients: The Predictive Role of Different Immunological Assays

Cells. 2024 Aug 8;13(16):1325. doi: 10.3390/cells13161325.

Abstract

Human cytomegalovirus (HCMV) infection remains a major complication for solid organ transplant recipients (SOTRs). The aim of this study was to evaluate the role of HCMV-specific T cell immunity measured at the time of the HCMV-DNA peak in predicting the spontaneous clearance of infection. The performance of cytokine flow cytometry using infected dendritic cells (CFC-iDC), infected cell lysate (CFC-iCL) and pp65 peptide pool (CFC-pp65 pool) as stimuli, as well as ELISPOT assays using infected cell lysate (ELISPOT-iCL) and the pp65 peptide pool (ELISPOT-pp65 pool), was analysed. Among the 40 SOTRs enrolled, 16 patients (40%) required antiviral treatment for an HCMV infection (Non-Controllers), while the others spontaneously cleared the infection (Controllers). At the HCMV-DNA peak, the number of HCMV-specific CD4+ T cells detected by the CFC-iDC, CFC-iCL and CFC-pp65 pool assays in Controllers was higher than that detected in Non-Controllers, while no difference was observed in terms of HCMV-specific CD8+ T cell response. The same trend was observed when the HCMV-specific T cell response was measured by ELISPOT-iCL and ELISPOT-pp65 pool. We observed that the CD4+ CFC-pp65 pool assay was the best predictor of self-resolving HCMV infection at the time of the HCVM-DNA peak. The CFC-pp65 pool assay is able to discriminate between CD4+ and CD8+ T cell responses and could be used in daily clinical practice.

Keywords: T cell response; human cytomegalovirus; immune assays; solid organ transplant recipients.

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cytokines / metabolism
  • Cytomegalovirus Infections* / immunology
  • Cytomegalovirus Infections* / virology
  • Cytomegalovirus* / immunology
  • DNA, Viral
  • Dendritic Cells / immunology
  • Enzyme-Linked Immunospot Assay
  • Female
  • Humans
  • Immunologic Tests / methods
  • Male
  • Middle Aged
  • Organ Transplantation / adverse effects
  • Transplant Recipients*

Substances

  • DNA, Viral
  • Cytokines