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Int J Mol Sci. 2019 Mar 20;20(6). pii: E1415. doi: 10.3390/ijms20061415.

Robust Identification of Suitable T-Cell Subsets for Personalized CMV-Specific T-Cell Immunotherapy Using CD45RA and CD62L Microbeads.

Author information

1
Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany. mangare.caroline@mh-hannover.de.
2
Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany. tischer-zimmermann.sabine@mh-hannover.de.
3
Integrated Research and Treatment Center (IFB-Tx), Hannover Medical School, 30625 Hannover, Germany. tischer-zimmermann.sabine@mh-hannover.de.
4
Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany. riese.sebastian@mh-hannover.de.
5
Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany. dragon.anna@mh-hannover.de.
6
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany. prinz.immo@mh-hannover.de.
7
Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany. blasczyk.rainer@mh-hannover.de.
8
Integrated Research and Treatment Center (IFB-Tx), Hannover Medical School, 30625 Hannover, Germany. blasczyk.rainer@mh-hannover.de.
9
Integrated Research and Treatment Center (IFB-Tx), Hannover Medical School, 30625 Hannover, Germany. maecker-kolhoff.britta@mh-hannover.de.
10
Department of Pediatric Hematology and Oncology, Hannover Medical School, 30625 Hannover, Germany. maecker-kolhoff.britta@mh-hannover.de.
11
Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany. eiz-vesper.britta@mh-hannover.de.
12
Integrated Research and Treatment Center (IFB-Tx), Hannover Medical School, 30625 Hannover, Germany. eiz-vesper.britta@mh-hannover.de.

Abstract

Viral infections and reactivations remain a serious obstacle to successful hematopoietic stem cell transplantation (HSCT). When antiviral drug treatment fails, adoptive virus-specific T-cell transfer provides an effective alternative. Assuming that naive T cells (TN) are mainly responsible for GvHD, methods were developed to generate naive T-cell-depleted products while preserving immune memory against viral infections. We compared two major strategies to deplete potentially alloreactive T cells: CD45RA and CD62L depletion and analyzed phenotype and functionality of the resulting CD45RA-/CD62L- naive T-cell-depleted as well as CD45RA⁺/CD62L⁺ naive T-cell-enriched fractions in the CMV pp65 and IE1 antigen model. CD45RA depletion resulted in loss of terminally differentiated effector memory T cells re-expressing CD45RA (TEMRA), and CD62L depletion in loss of central memory T cells (TCM). Based on these differences in target cell-dependent and target cell-independent assays, antigen-specific T-cell responses in CD62L-depleted fraction were consistently 3⁻5 fold higher than those in CD45RA-depleted fraction. Interestingly, we also observed high donor variability in the CD45RA-depleted fraction, resulting in a substantial loss of immune memory. Accordingly, we identified donors with expected response (DER) and unexpected response (DUR). Taken together, our results showed that a naive T-cell depletion method should be chosen individually, based on the immunophenotypic composition of the T-cell populations present.

KEYWORDS:

cytomegalovirus (CMV); donor lymphocyte infusions (DLIs); graft versus host disease (GvHD); naive T-cell depletion

PMID:
30897843
PMCID:
PMC6471767
DOI:
10.3390/ijms20061415
[Indexed for MEDLINE]
Free PMC Article

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