Innate and Adaptive Immune Correlates of Chronic and Self-limiting EBV DNAemia in Solid-organ Transplant Recipients.
Adaptive Immunity
Adult
Aged
CD11c Antigen
/ blood
CD4-Positive T-Lymphocytes
/ immunology
Chronic Disease
Cross-Sectional Studies
DNA, Viral
/ blood
Dendritic Cells
/ immunology
Epstein-Barr Virus Infections
/ blood
Female
Herpesvirus 4, Human
/ genetics
Host-Pathogen Interactions
Humans
Immunity, Innate
Interferon-gamma
/ blood
Male
Middle Aged
Opportunistic Infections
/ blood
Organ Transplantation
/ adverse effects
Treatment Outcome
Viral Load
Young Adult
Journal
Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
pubmed:
28
1
2020
medline:
10
2
2021
entrez:
28
1
2020
Statut:
ppublish
Résumé
Epstein-Barr virus (EBV) DNAemia is a major risk factor for posttransplant lymphoproliferative disorder; however, immune correlates of EBV DNAemia in the transplant setting are limited. Peripheral blood mononuclear cells were collected from 30 transplant recipients with self-limiting EBV DNAemia (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. Unsupervised analysis of the innate compartment (CD3CD19 cells) identified 5 CD11c clusters at higher abundance in the SLD group (false discovery rate ≤ 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 (false discovery rate ≤ 1%), which expressed CD45RA, CCR7, CD27, CD28, and CD40L-suggestive of a naive T cell (TN). Manual biaxial gating confirmed increased frequencies of conventional dendritic cells (3.1% versus 2.1%; P = 0.023) and CD4 TN (4.4% versus 1.9%; P = 0.018) among those with SLD. Last, frequencies of interferon-γ-producing EBV-specific CD4 T cells were significantly lower in the CD group relative to those with SLD (4243 versus 250 cells/10 cells; P = 0.015). CD is associated with a reduction of CD11c cells, CD4 TN, and interferon-γ-producing EBV-specific CD4 T cells, suggesting an interplay between innate and adaptive immune compartments may be important for regulating EBV DNAemia.
Sections du résumé
BACKGROUND
Epstein-Barr virus (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 EBV DNAemia (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 ≤ 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 (false discovery rate ≤ 1%), which expressed CD45RA, CCR7, CD27, CD28, and CD40L-suggestive of a naive T cell (TN). Manual biaxial gating confirmed increased frequencies of conventional dendritic cells (3.1% versus 2.1%; P = 0.023) and CD4 TN (4.4% versus 1.9%; P = 0.018) among those with SLD. Last, frequencies of interferon-γ-producing EBV-specific CD4 T cells were significantly lower in the CD group relative to those with SLD (4243 versus 250 cells/10 cells; P = 0.015).
CONCLUSIONS
CD is associated with a reduction of CD11c cells, CD4 TN, and interferon-γ-producing EBV-specific CD4 T cells, suggesting an interplay between innate and adaptive immune compartments may be important for regulating EBV DNAemia.
Identifiants
pubmed: 31985732
doi: 10.1097/TP.0000000000003130
pii: 00007890-202011000-00028
doi:
Substances chimiques
CD11c Antigen
0
DNA, Viral
0
IFNG protein, human
0
Interferon-gamma
82115-62-6
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2373-2382Références
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