Robust Identification of Suitable T-Cell Subsets for Personalized CMV-Specific T-Cell Immunotherapy Using CD45RA and CD62L Microbeads.
Int J Mol Sci
; 20(6)2019 Mar 20.
Article
en En
| MEDLINE
| ID: mdl-30897843
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 CD45RAâº/CD62L⺠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 3â»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.
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Texto completo:
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Banco de datos:
MEDLINE
Asunto principal:
Subgrupos de Linfocitos T
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Antígenos Comunes de Leucocito
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Selectina L
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Inmunoterapia
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article