Deep Profiling of the CD8+ T-cell Compartment Identifies Activated Cell Subsets and Multifunctional Responses Associated With Control of Cytomegalovirus Viremia

Transplantation
Victor H FerreiraAtul Humar

Abstract

Human cytomegalovirus (HCMV) is a common opportunistic pathogen in transplant recipients. Patterns of viremia and reactivation are influenced by the host immune response, including CD8 T cells. However, the cellular deficits or phenotypic differences that account for differential outcomes during HCMV viremia are incompletely understood. Peripheral blood mononuclear cells were collected from 20 transplant recipients (10 viremia controllers and 10 noncontrollers) at onset of HCMV viremia and 4 weeks postonset. We used mass cytometry to perform in-depth characterization of cell surface and intracellular CD8 T cell markers and to compare frequencies of these cells between groups. Deep profiling identified 2 central memory T cell subsets at onset and 5 terminally differentiated memory T (TEMRA) cell subsets at 4 weeks that were associated with control of HCMV viremia, in addition to 6 TEMRA subsets at onset and 4 weeks associated with relapsing or remitting HCMV viremia. In general, CD8 T-cell clusters associated with poorly controlled HCMV viremia lacked markers of activation or terminal differentiation including CD38, CD69, CD25, CD57, and HLA-DR. We also measured the production of 8 HCMV-specific effector molecules (TNFα, IFNγ, i...Continue Reading

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Citations

Aug 28, 2020·Frontiers in Immunology·Julienne KnolleMonika C Brunner-Weinzierl
May 22, 2020·JCI Insight·Anita K McElroyChristina F Spiropoulou
Aug 6, 2019·Frontiers in Immunology·Jose Ramón Vidal-CastiñeiraCarmen Díaz-Corte
Oct 30, 2021·Frontiers in Cellular and Infection Microbiology·Jose MateusAdriana Cuéllar

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