Early exposure to interleukin-21 limits rapidly generated anti-Epstein-Barr virus T-cell line differentiation.
| Title: | Early exposure to interleukin-21 limits rapidly generated anti-Epstein-Barr virus T-cell line differentiation. |
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| Authors: | Orio J; Hôpital Maisonneuve-Rosemont Research Centre, Quebec, Canada.; Carli C; Hôpital Maisonneuve-Rosemont Research Centre, Quebec, Canada.; Janelle V; Hôpital Maisonneuve-Rosemont Research Centre, Quebec, Canada.; Giroux M; Hôpital Maisonneuve-Rosemont Research Centre, Quebec, Canada.; Taillefer J; Hôpital Maisonneuve-Rosemont Research Centre, Quebec, Canada.; Goupil M; Hôpital Maisonneuve-Rosemont Research Centre, Quebec, Canada.; Richaud M; Hôpital Maisonneuve-Rosemont Research Centre, Quebec, Canada.; Roy DC; Hôpital Maisonneuve-Rosemont Research Centre, Quebec, Canada; Hematology-Oncology Division, Hôpital Maisonneuve-Rosemont, Quebec, Canada; Department of Medicine, University of Montréal, Quebec, Canada.; Delisle JS; Hôpital Maisonneuve-Rosemont Research Centre, Quebec, Canada; Hematology-Oncology Division, Hôpital Maisonneuve-Rosemont, Quebec, Canada; Department of Medicine, University of Montréal, Quebec, Canada. Electronic address: js.delisle@umontreal.ca. |
| Source: | Cytotherapy [Cytotherapy] 2015 Apr; Vol. 17 (4), pp. 496-508. Date of Electronic Publication: 2015 Feb 03. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: England NLM ID: 100895309 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-2566 (Electronic) Linking ISSN: 14653249 NLM ISO Abbreviation: Cytotherapy Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2013- : London : Elsevier; Original Publication: Oxford, England : ISIS Medical Media, c1999- |
| MeSH Terms: | Adoptive Transfer*; Epstein-Barr Virus Infections/*therapy ; Herpesvirus 4, Human/*immunology ; Interleukins/*immunology ; Lymphocyte Activation/*immunology ; Neoplasms/*therapy ; T-Lymphocyte Subsets/*immunology; Cell Differentiation/drug effects ; Cell Differentiation/immunology ; Neoplasms/virology ; T-Lymphocyte Subsets/transplantation ; Cell Line ; Humans ; Interleukin-21 |
| Abstract: | Background Aims: The adoptive transfer of ex vivo-expanded Epstein-Barr virus (EBV)-specific T-cell lines is an attractive strategy to treat EBV-related neoplasms. Current evidence suggests that for adoptive immunotherapy in general, clinical responses are superior if the transferred cells have not reached a late or terminal effector differentiation phenotype before infusion. The cytokine interleukin (IL)-21 has shown great promise at limiting late T-cell differentiation in vitro, but this remains to be demonstrated in anti-viral T-cell lines.; Methods: We adapted a clinically validated protocol to rapidly generate EBV-specific T-cell lines in 12 to 14 days and tested whether the addition of IL-21 at the initiation of the culture would affect T-cell expansion and differentiation.; Results: We generated clinical-scale EBV-restricted T-cell line expansion with balanced T-cell subset ratios. The addition of IL-21 at the beginning of the culture decreased both T-cell expansion and effector memory T-cell accumulation, with a relative increase in less-differentiated T cells. Within CD4 T-cell subsets, exogenous IL-21 was notably associated with the cell surface expression of CD27 and high KLF2 transcript levels, further arguing for a role of IL-21 in the control of late T-cell differentiation.; Conclusions: Our results show that IL-21 has profound effects on T-cell differentiation in a rapid T-cell line generation protocol and as such should be further explored as a novel approach to program anti-viral T cells with features associated with early differentiation and optimal therapeutic efficacy.; (Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.) |
| Contributed Indexing: | Keywords: CD27; Epstein-Barr virus; IL-21; T cell; T-cell memory; adoptive immunotherapy |
| Substance Nomenclature: | 0 (Interleukins); MKM3CA6LT1 (Interleukin-21) |
| Entry Date(s): | Date Created: 20150210 Date Completed: 20160321 Latest Revision: 20250103 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.jcyt.2014.12.009 |
| PMID: | 25661862 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't