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The “ABC” of Virus-Specific T Cell Immunity in Solid Organ Transplantation

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Transplant patients are at increased risk of viral complications due to impaired control of viral replication, resulting from HLA mismatching between graft and host and the immunosuppression needed to avert alloimmune reactions. In the past decade, quantitative viral load measurements have become widely available to identify patients at risk and to inform treatment decisions with respect to immunosuppressive drugs and antiviral therapies. Because viral loads are viewed as the result of viral replication and virus-specific immune control, virus-specific T cell monitoring has been explored to optimize management of adenovirus, BK polyomavirus and cytomegalovirus (“ABC”) in transplant patients. Although most studies are descriptive using different technologies, the overall results show that the quantity and quality of virus-specific T cells inversely correlate with viral replication, whereby strong cellular immune responses are associated with containment of viral replication. The key obstacles to the introduction of assays for virus-specific T cells into clinical practice is the definition of reliable cutoffs for clinical decision making, the poor negative predictive value of some assays, and the absence of interventional trials justifying changes of antiviral treatment or immunosuppression. More clinical research is needed using optimized assays and targets before standardization and commutability can be envisaged as achieved for viral load testing.

Abbreviations

ADV
adenovirus
BKPyV
BK polyomavirus
CMV
cytomegalovirus
EBV
Epstein-Barr virus
ELISA
enzyme-linked immunosorbent assay
ELISpot
enzyme-linked immunospot
HSCT
hematopoietic stem-cell transplantation
IFN-γ
interferon-γ
ICS
intracellular cytokine staining
LTag
large T antigen
PBMC
peripheral blood mononuclear cells
PTLD
posttransplant lymphoproliferative disorder
PyVAN
BKPyV-associated nephropathy
SOT
solid organ transplantation
VZV
varicella zoster virus

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