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| Content Provider | Springer Nature Link |
|---|---|
| Author | Weist, B. J. D. Schmueck, M. Fuehrer, H. Sattler, A. Reinke, P. Babel, N. |
| Copyright Year | 2014 |
| Abstract | Reactivation of polyomavirus BK (BKV) infection represents a severe complication in kidney transplant (KTX) patients. We previously reported an association between a declining BK viral load and the reconstitution of CD4+ T cell BKV-specific immunity in patients following kidney transplantation. However, the specific contribution of CD4+ T cells in the regulation of BKV-replication is unknown. Nevertheless, in vitro enrichment of BKV-specific T cells and subsequent adoptive T cell transfer may improve the restoration of immune competence in KTX patients with BKV infection. To date, strategies to capture human BKV-specific T cells with the ensuing expansion to clinically useful numbers are lacking. Here, we demonstrated a comprehensive flow cytometric analysis of the BKV-specific T cell response that permits access to the majority of T cells specific for immunodominant BKV antigens. A full-spectrum evaluation of the BKV-specific T cell response was performed by stimulating peripheral blood mononuclear cells (PBMC) with a mixture of BKV immunodominant peptide pools at varying concentrations and measuring activation marker expression and cytokine secretion. We also examined the effects of co-stimulation and PBMC resting time prior to activation. We defined the narrow range of stimulation conditions that permit the capture and expansion of functional BKV-specific T cell lines. The generated BKV-specific T cell lines showed the highest specificity and functionality when the T cells were captured according to IFNγ-secretion. This study highlights the multifunctional and cytolytic BKV-specific CD4+ T cells as a dominant population within the generated T cell product. This method offers a novel approach for the generation of BKV-specific T cell lines for adoptive immunotherapy and underscores the critical role of CD4+ T cells in the clearance of BKV. |
| Starting Page | 395 |
| Ending Page | 408 |
| Page Count | 14 |
| File Format | |
| ISSN | 03008584 |
| Journal | Medical Microbiology and Immunology |
| Volume Number | 203 |
| Issue Number | 6 |
| e-ISSN | 14321831 |
| Language | English |
| Publisher | Springer Berlin Heidelberg |
| Publisher Date | 2014-07-23 |
| Publisher Place | Berlin/Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | BKV CD4 T cell Adoptive Kidney transplantation Medical Microbiology Immunology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology Microbiology (medical) |
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