Analysis of the functional WT1-specific T-cell repertoire in healthy donors reveals a discrepancy between CD4+ and CD8+ memory formation
The Wilms’ tumour-1 (WT1) protein is considered a prime target for cancer immunotherapy based on its presumptive immunogenicity and widespread expression across a variety of malignancies. However, little is known about the naturally occurring WT1-specific T-cell repertoire because self-derived antig...
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John Wiley & Sons, Ltd
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515135/ |
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pubmed-45151352016-02-11 Analysis of the functional WT1-specific T-cell repertoire in healthy donors reveals a discrepancy between CD4+ and CD8+ memory formation Schmied, Sabine Gostick, Emma Price, David A Abken, Hinrich Assenmacher, Mario Richter, Anne Original Articles The Wilms’ tumour-1 (WT1) protein is considered a prime target for cancer immunotherapy based on its presumptive immunogenicity and widespread expression across a variety of malignancies. However, little is known about the naturally occurring WT1-specific T-cell repertoire because self-derived antigens typically elicit low frequency responses that challenge the sensitivity limits of current detection techniques. In this study, we used highly efficient cell enrichment procedures based on CD137, CD154, and pHLA class I tetramer staining to conduct a detailed analysis of WT1-specific T cells from the peripheral blood. Remarkably, we detected WT1-specific CD4+ and CD8+ T-cell populations in the vast majority of healthy individuals. Memory responses specific for WT1 were commonly present in the CD4+ T-cell compartment, whereas WT1-specific CD8+ T cells almost universally displayed a naive phenotype. Moreover, memory CD4+ and naive CD8+ T cells with specificity for WT1 were found to coexist in some individuals. Collectively, these findings suggest a natural discrepancy between the CD4+ and CD8+ T-cell lineages with respect to memory formation in response to a self-derived antigen. Nonetheless, WT1-specific T cells from both lineages were readily activated ex vivo and expanded in vitro, supporting the use of strategies designed to exploit this expansive reservoir of self-reactive T cells for immunotherapeutic purposes. John Wiley & Sons, Ltd 2015-08 2015-06-19 /pmc/articles/PMC4515135/ /pubmed/25882672 http://dx.doi.org/10.1111/imm.12472 Text en © 2015 John Wiley & Sons Ltd http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Schmied, Sabine Gostick, Emma Price, David A Abken, Hinrich Assenmacher, Mario Richter, Anne |
| spellingShingle |
Schmied, Sabine Gostick, Emma Price, David A Abken, Hinrich Assenmacher, Mario Richter, Anne Analysis of the functional WT1-specific T-cell repertoire in healthy donors reveals a discrepancy between CD4+ and CD8+ memory formation |
| author_facet |
Schmied, Sabine Gostick, Emma Price, David A Abken, Hinrich Assenmacher, Mario Richter, Anne |
| author_sort |
Schmied, Sabine |
| title |
Analysis of the functional WT1-specific T-cell repertoire in healthy donors reveals a discrepancy between CD4+ and CD8+ memory formation |
| title_short |
Analysis of the functional WT1-specific T-cell repertoire in healthy donors reveals a discrepancy between CD4+ and CD8+ memory formation |
| title_full |
Analysis of the functional WT1-specific T-cell repertoire in healthy donors reveals a discrepancy between CD4+ and CD8+ memory formation |
| title_fullStr |
Analysis of the functional WT1-specific T-cell repertoire in healthy donors reveals a discrepancy between CD4+ and CD8+ memory formation |
| title_full_unstemmed |
Analysis of the functional WT1-specific T-cell repertoire in healthy donors reveals a discrepancy between CD4+ and CD8+ memory formation |
| title_sort |
analysis of the functional wt1-specific t-cell repertoire in healthy donors reveals a discrepancy between cd4+ and cd8+ memory formation |
| description |
The Wilms’ tumour-1 (WT1) protein is considered a prime target for cancer immunotherapy based on its presumptive immunogenicity and widespread expression across a variety of malignancies. However, little is known about the naturally occurring WT1-specific T-cell repertoire because self-derived antigens typically elicit low frequency responses that challenge the sensitivity limits of current detection techniques. In this study, we used highly efficient cell enrichment procedures based on CD137, CD154, and pHLA class I tetramer staining to conduct a detailed analysis of WT1-specific T cells from the peripheral blood. Remarkably, we detected WT1-specific CD4+ and CD8+ T-cell populations in the vast majority of healthy individuals. Memory responses specific for WT1 were commonly present in the CD4+ T-cell compartment, whereas WT1-specific CD8+ T cells almost universally displayed a naive phenotype. Moreover, memory CD4+ and naive CD8+ T cells with specificity for WT1 were found to coexist in some individuals. Collectively, these findings suggest a natural discrepancy between the CD4+ and CD8+ T-cell lineages with respect to memory formation in response to a self-derived antigen. Nonetheless, WT1-specific T cells from both lineages were readily activated ex vivo and expanded in vitro, supporting the use of strategies designed to exploit this expansive reservoir of self-reactive T cells for immunotherapeutic purposes. |
| publisher |
John Wiley & Sons, Ltd |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515135/ |
| _version_ |
1613252231690190848 |