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Transplantation. 2018 Jul 18. doi: 10.1097/TP.0000000000002373. [Epub ahead of print]

Deep Profiling of the CD8+ T cell Compartment identifies Activated cell subsets and Multifunctional Responses Associated with Control of Cytomegalovirus Viremia.

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1
Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Canada.

Abstract

BACKGROUND:

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.

METHODS:

PBMCs were collected from 20 transplant recipients (10 viremia controllers and 10 noncontrollers) at onset of HCMV viremia and 4-weeks post. We utilized 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.

RESULTS:

Deep profiling identified 2 TCM subsets at onset and 5 TEMRA 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, IL2, granzyme B, perforin, MIP1β, IL10 and CD107a) in CD8 T cells. Viremia controllers had greater diversity of HCMV-specific multi-functional responses at both time points, including significantly higher frequencies of HCMV-specific TNFαIFNγ CD8 T cells at onset. These multifunctional cells had a phenotype consistent with activated TEM/TEMRA cells.

CONCLUSIONS:

Uncontrolled CMV viremia is associated with specific clusters of memory T cell subsets and lower frequencies of HCMV-specific multifunctional CD8 T cells.

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