Analysis and Fine Specificity of the HCMV-Specific Cell-Free and Cell-Associated Antibody-Dependent Cellular Phagocytosis (ADCP) Responses in Lung Transplant Recipients

Int J Mol Sci. 2021 Jul 30;22(15):8206. doi: 10.3390/ijms22158206.

Abstract

Human Cytomegalovirus (HCMV) may cause severe infections in transplant recipients. HCMV-replication can be limited by HCMV-specific antibody responses. The impact of the antibody-dependent cellular phagocytosis (ADCP) on inhibition of HCMV-replication in natural infections has not been clarified. Therefore, we investigated the HCMV-specific ADCP response in a study cohort of lung-transplant recipients (LTRs) with different donor (D) and recipient (R) HCMV-serostatus. Follow-up plasma samples from 39 non/low-viremic and 36 highly viremic (>1000 HCMV copies/mL plasma) LTRs were collected for one (R+ LTRs) or two (D+/R- LTRs) years post-transplantation. The HCMV-specific ADCP responses were assessed by focal expansion assays (FEA) and flow-cytometry. In all LTRs, ADCP responses were detected against HCMV-infected cells and cell-free virions. When measured in fibroblasts as well as with cell-free virus, the HCMV-specific ADPC response was higher in LTRs than in HCMV-seropositive healthy controls. In D+/R- LTRs, a significant ADCP response developed over time after the receipt of an HCMV positive lung, and a level of <19 IE+ cells/focus in the FEA on fibroblasts was associated with further protection from high-level viremia. Taken together, a strong HCMV-specific ADCP response is elicited in transplant recipients, which may contribute to protection from high-level viremia in primary HCMV infection.

Keywords: ADCP; HCMV; antibody; phagocytosis.

MeSH terms

  • Cells, Cultured
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / etiology
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • Female
  • Humans
  • Immunoglobulin G / immunology*
  • Lung Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Phagocytosis*
  • THP-1 Cells
  • Viral Load
  • Wound Infection / etiology
  • Wound Infection / immunology*
  • Wound Infection / virology

Substances

  • Immunoglobulin G