UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

In Vivo Gene Delivery to Lymph Node Stromal Cells Leads to Transgene-specific CD8+ T Cell Anergy in Mice

Ciré, S; Da Rocha, S; Ferrand, M; Collins, MK; Galy, A; (2016) In Vivo Gene Delivery to Lymph Node Stromal Cells Leads to Transgene-specific CD8+ T Cell Anergy in Mice. Molecular Therapy , 24 (11) pp. 1965-1973. 10.1038/mt.2016.168. Green open access

[img]
Preview
Text
mt2016168a.pdf - ["content_typename_Accepted version" not defined]

Download (804kB) | Preview

Abstract

Lymph node stromal cells play a role in self-tolerance by presenting tissue antigens to T cells. Yet, immunomodulatory properties of lymphoid tissue stroma, particularly toward CD4+ T cells, remain insufficiently characterized by lack of tools to target antigens for presentation by stromal cells. A lentiviral vector was therefore designed for antigen delivery to MHC class II(+) cells of nonhematopoietic origin. Following intravenous vector delivery, the transgene was detected in lymph node gp38+ stromal cells which were CD45- MHCII+ and partly positive for CD86 and CTLA4 or B7-H4. The transgene was not detected in classical dendritic cells of lymph nodes or spleen. Transgene-specific CD4+ and CD8+ T cell responses were primed and regulatory T cells were also induced but effector T cell response did not develop, even after a peptide boost. Antigen-specific CD8+ T cells were not cytolytic in vivo. Thus, expressing a neo-antigen in MHC-II+ lymph node stroma seems to trigger blunt CD4 T cell responses leading to antigen-specific CD8+ T cell anergy. These results open up new perspectives to further characterize lymph node stromal cell functional properties and to develop gene transfer protocols targeting lymph node stroma to induce peripheral tolerance.

Type: Article
Title: In Vivo Gene Delivery to Lymph Node Stromal Cells Leads to Transgene-specific CD8+ T Cell Anergy in Mice
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/mt.2016.168
Publisher version: http://dx.doi.org/10.1038/mt.2016.168
Language: English
Additional information: Copyright © 2016. This manuscript version is published under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International licence (CC BY-NC-ND 4.0). This licence allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licences are available at http://creativecommons.org/licenses/by/4.0. Access may be initially restricted by the publisher.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1514940
Downloads since deposit
45Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item