Intrathymic injection of lentiviral vector curtails the immune response in the periphery of normal mice

Gottrand, Gaëlle, Taleb. Kahina, Ragon, Isabelle, Bergot, Anne-Sophie, Goldstein, Jeremie D. and Marodon, Gilles (2012) Intrathymic injection of lentiviral vector curtails the immune response in the periphery of normal mice. Journal of Gene Medicine, 14 2: 90-99. doi:10.1002/jgm.1650


Author Gottrand, Gaëlle
Taleb. Kahina
Ragon, Isabelle
Bergot, Anne-Sophie
Goldstein, Jeremie D.
Marodon, Gilles
Title Intrathymic injection of lentiviral vector curtails the immune response in the periphery of normal mice
Journal name Journal of Gene Medicine   Check publisher's open access policy
ISSN 1099-498X
1521-2254
Publication date 2012
Year available 2012
Sub-type Article (original research)
DOI 10.1002/jgm.1650
Volume 14
Issue 2
Start page 90
End page 99
Total pages 10
Place of publication Hoboken, NJ United States
Publisher Jossey Bass, Ed. and Pub.
Collection year 2013
Language eng
Subject 1311 Genetics
1312 Molecular Biology
1313 Molecular Medicine
2716 Genetics (clinical)
3002 Drug Discovery
Abstract Background: Gene transfer in the thymus, based on HIV-derived lentiviral vectors, is a promising avenue for modulation of T cell selection and autoimmunity. However, the impact of intrathymic (IT) injections on an antigen-specific immune response elicited in the periphery of normal mice has not been investigated yet. Methods: Highly concentrated stocks of lentiviral vectors expressing the soluble form of hemaglutinin of the influenza virus (LvHA) were injected in the thymus of normal BALB/c mice. The CD4 and CD8-mediated immune responses to HA after peripheral immunization were measured by various parameters. Results: We first show that a lentiviral vector expressing the luciferase was detected for at least 2months after IT-injections. We then show that the LvHA vector could elicit a functional CD4- and CD8-T cell-mediated immune responses in the peripheral lymphoid organs of BALB/c mice. IT-injection of the LvHA vector significantly curbed this response: lower numbers of transferred HA-specific CD4 + T cells were found in LvHA-injected compared to control animals. Furthermore, lower frequencies of HA-specific CD8 + T cells, interferon γ-producing cells and cytotoxic cells were detected from 3weeks to 3months in LvHA-injected mice compared to controls. However, these reduced CD8-mediated responses were not increased after depletion of CD25 + cells in vitro or in vivo. Conclusions: The results obtained in the present study show that injection of the LvHA lentiviral vector significantly curtailed the immune response to the same antigen in the periphery. Increased selection of HA-specific regulatory T cells and negative selection of HA-specific CD8 + T cell precursors may explain the results. Our work establish the feasibility of IT-injections of lentiviral vectors to manipulate T cell tolerance in the thymus of normal mice, for basic and pre-clinical research.
Keyword Gene transfer
Lentiviral vector
Thymus
Tolerance
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute Publications
 
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