T-cell receptor transfer for boosting Hiv-1-specific T-cell immunity in Hiv-1-infected patients
Strategies to cure HIV-1 infection require the eradication of viral reservoirs. An innovative approach for boosting the cytotoxic T-lymphocyte response is the transfer of T-cell receptors (TCRs). Previously, we have shown that electroporation of TCR-encoding mRNA is able to reprogram CD8+ T cells de...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
10 September 2016
|
| In: |
AIDS <London>
Year: 2016, Volume: 30, Issue: 14, Pages: 2149-2158 |
| ISSN: | 1473-5571 |
| DOI: | 10.1097/QAD.0000000000001176 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1097/QAD.0000000000001176 Verlag, kostenfrei, Volltext: https://insights.ovid.com/pubmed?pmid=27258398 
|
| Author Notes: | Christiane Mummert, Christian Hofmann, Angela G. Hückelhoven, Silke Bergmann, Sandra M. Mueller-Schmucker, Ellen G. Harrer, Jan Dörrie, Niels Schaft and Thomas Harrer |
| Summary: | Strategies to cure HIV-1 infection require the eradication of viral reservoirs. An innovative approach for boosting the cytotoxic T-lymphocyte response is the transfer of T-cell receptors (TCRs). Previously, we have shown that electroporation of TCR-encoding mRNA is able to reprogram CD8+ T cells derived from healthy donors. So far, it is unknown whether the transfer of HIV-1-specific TCRs is capable to reprogram CD8+ T cells of HIV-1-infected patients. To assess the efficiency of TCR-transfer by mRNA electroporation and the functionality of reprogramed T cells in HIV-1-infected patients, we performed an in-vitro analysis of TCR-transfer into T cells from HIV-1-infected patients in various stages of disease and from healthy controls. Peripheral blood mononuclear cells from 16 HIV-1-infected patients (nine HLA-A*02-positive, seven HLA-A*02-negative) and from five healthy controls were electroporated with mRNA-constructs encoding TCRs specific for the HLA-A*02/HIV-1-gag p17 epitope SLYNTVATL (SL9). Functionality of the TCRs was measured by γIFN-ELISpot assays. SL9/TCR transfection into peripheral blood mononuclear cells from both HLA-A*02-positive and HLA-A*02-negative HIV-1-infected patients and from healthy blood donors reprogramed T cells for recognition of SL9-presenting HLA-A*02-positive cells in γIFN-ELISpot assays. SL9/TCR-transfer into T cells from an immunodeficient AIDS patient could induce recognition of SL9-expressing target cells only after reversion of T-cell dysfunction by antiretroviral therapy. The transfer of HIV-1-p17-specific TCRs into T cells is functional both in HIV-1-infected patients as well as in healthy blood donors. TCR-transfer is a promising method to boost the immune system against HIV-1. |
|---|---|
| Item Description: | Gesehen am 02.01.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1473-5571 |
| DOI: | 10.1097/QAD.0000000000001176 |