Innate and adaptive immune correlates of chronic and self-limiting Epstein-Barr Virus (EBV) DNAemia in solid-organ transplant recipients
Ferreira, V.H., Batist, J., Humar, A.
Background: EBV DNAemia is a major risk factor for posttransplant lymphoproliferative disorder; however, immune correlates of EBV DNAemia in the transplant setting are limited.
Methods: Peripheral blood mononuclear cells were collected from 30 transplant recipients with self-limiting (SLD;n=11) or chronic EBV DNAemia (CD;n=19) at enrollment and 4-8 weeks later. Mass cytometry was used to characterize innate and T-cell immune correlates of EBV DNAemia. Furthermore, flow cytometry was used to measure the frequency of EBV-specific T-cell responses between groups following stimulation with an EBV-infected cell lysate.
Results: Unsupervised analysis of the innate compartment (CD3CD19 cells) identified 5 CD11c clusters at higher abundance in the SLD group (false discovery rate (FDR)≤ 1%). These clusters expressed CD11b, CD45RO, CD14, CD123, CD127 and CD38, among others. Unsupervised profiling of the T-cell compartment (CD3CD19) revealed 2 CD4 T-cell clusters at higher frequency among those with SLD (FDR ≤ 1%), which expressed CD45RA, CCR7, CD27, CD28 and CD40L - suggestive of a naïve T-cell (TN). Manual biaxial gating confirmed increased frequencies of conventional dendritic cells (3.1% vs. 2.1%, p=0.023) and CD4 TN (4.4% vs. 1.9%, p=0.018) among those with SLD. Lastly, frequencies of interferon-gamma (IFNγ)-producing EBV-specific CD4 T-cells were significantly lower in the CD group relative to those with SLD (4243 vs. 250 cells/10 cells, p=0.015).
Conclusions: Chronic EBV DNAemia is associated with a reduction of CD11c cells, CD4 TN and IFNγ-producing EBV-specific CD4 T-cells, suggesting an interplay between innate and adaptive immune compartments may be important for regulating EBV DNAemia.
Ferreira, V.H., Batist, J., Humar, A. "Innate and adaptive immune correlates of chronic and self-limiting Epstein-Barr Virus (EBV) DNAemia in solid-organ transplant recipients" Transplantation (2020): DOI: 10.1097/TP.0000000000003130