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

Authors :
Mangare C
Tischer-Zimmermann S
Riese SB
Dragon AC
Prinz I
Blasczyk R
Maecker-Kolhoff B
Eiz-Vesper B
Source :
International journal of molecular sciences [Int J Mol Sci] 2019 Mar 20; Vol. 20 (6). Date of Electronic Publication: 2019 Mar 20.
Publication Year :
2019

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 (T <subscript>N</subscript> ) 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 <superscript>-</superscript> /CD62L <superscript>-</superscript> 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 (T <subscript>EMRA</subscript> ), and CD62L depletion in loss of central memory T cells (T <subscript>CM</subscript> ). 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.<br />Competing Interests: The authors declare no conflict of interest.

Details

Language :
English
ISSN :
1422-0067
Volume :
20
Issue :
6
Database :
MEDLINE
Journal :
International journal of molecular sciences
Publication Type :
Academic Journal
Accession number :
30897843
Full Text :
https://doi.org/10.3390/ijms20061415