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Published in:

01-09-2003 | Molecular Diagnostics

Clinical Utility of Tetramer-Based Immune Monitoring in Allogeneic Stem Cell Transplantation

Authors: Dr Jan W. Gratama, Jan J. Cornelissen

Published in: BioDrugs | Issue 5/2003

Abstract

The construction and use of Class I human leucocyte antigen (HLA) tetramers has, for the first time, allowed the direct enumeration of CD8⁺ T lymphocytes specific for the antigen of interest. Tetramer staining can be combined with functional assays of antigen-specific T cells measuring their production of intracellular cytokines after short-term stimulation with antigen. The advantages of flow cytometric tetramer-based assays are their short turn-around time and their amenability to standardisation. Currently, their main limitation is that only a limited number of Class I HLA tetramers are available. This situation may bias the information derived from such studies. Nevertheless, clinically useful information has been obtained in tetramer-based studies of the regeneration of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)-specific CD8⁺ T cells after allogeneic stem cell transplantation (SCT).

Following myeloablative cytoreductive therapy and SCT, a period of deep cellular immunodeficiency follows until the donor-derived immune system has sufficiently regenerated. As a result of the lack of immunosurveillance, endogenous viruses such as CMV and EBV may reactivate and cause disease. In order to prevent these complications, pre-emptive therapeutic interventions are made, in which antiviral treatment is administered based on frequent viral load measurements. In this way, overtreatment associated with prophylactic strategies is reduced; however, a subgroup of patients developing recurrent reactivations and/or disease remains. Interventions aimed at the prevention of graft versus host disease (GVHD) and the reduction of its severity greatly reduce the rate of (virus-specific) T-cell reconstitution and hence, increase the frequency and severity of viral reactivations. Specifically, T-cell depletion of SCT and the use of antithymocyte globulin as part of the conditioning regimen reduces the (virus-specific) T lymphocytes transferred with the graft, which otherwise would have contributed to the first phase of T-cell regeneration post-SCT. Consequently, patients whose CMV-and EBV-specific CD8⁺ T cells fail to regenerate to levels detectable by tetramer-based flow cytometry during the first 3–6 months post-SCT were at highly increased risk for CMV disease and EBV⁺ B-lymphoproliferative disease, respectively. Furthermore, delayed reconstitution of the CD4⁺ T-cell compartment results in the lack of adequate help for the generation of sufficient antiviral CD8⁺ T cells. Conversely, adoptive immunotherapy using CMV-or EBV-specific T cells results in the swift restoration of virus-specific T-cell immunity and the reduction of viral load, unless corticosteroids have to be administered to treat concurrent GVHD. Studies have shown the clinical utility of tetramer-based immune monitoring in the setting of allogeneic SCT and indicate that such assays, extended by functional studies of the virus-specific T cells, may constitute a valuable extension of current viral load monitoring strategies.

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Title: Clinical Utility of Tetramer-Based Immune Monitoring in Allogeneic Stem Cell Transplantation
Authors: Dr Jan W. Gratama
Jan J. Cornelissen
Publication date: 01-09-2003
Publisher: Springer International Publishing
Published in: BioDrugs / Issue 5/2003
Print ISSN: 1173-8804
Electronic ISSN: 1179-190X
DOI: https://doi.org/10.2165/00063030-200317050-00003

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Clinical Utility of Tetramer-Based Immune Monitoring in Allogeneic Stem Cell Transplantation

Abstract

Keynote webinar | Spotlight on medication adherence

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Abstract

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