In Vivo Administration of a PKA Type I Inhibitor (Rp-8-Br-cAMPS) Restores T-Cell Responses in Retrovirus-Infected Mice
Btissam Nayjib§, 1, Mustapha Zeddou§, 1, Pierre Drion2, Jacques Boniver3, Kjetil Tasken4, Souad Rahmouni*, Michel Moutschen1
Identifiers and Pagination:Year: 2008
First Page: 20
Last Page: 24
Publisher Id: TOIJ-1-20
Article History:Received Date: 21/01/2008
Revision Received Date: 5/03/2008
Acceptance Date: 24/03/2008
Electronic publication date: 15/4/2008
Collection year: 2008
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Murine AIDS (MAIDS) is caused by infection with the murine leukemia retrovirus RadLV-Rs and is characterized by T-cell anergy and severe immunodeficiency with increased susceptibilty to several experimental opportunistic infections as observed in HIV infection. T cell anergy is associated with an increase of intracellular cAMP level, triggering a multistep pathway involving activation of PKA type I and resulting in inhibition of proximal TCR signaling. We have previously demonstrated that blocking PKA type I using the selective inhibitor Rp-8-Br-cAMPS, restores T-cell function in vitro in MAIDS as well as in HIV infection. In the present report, we investigated the effect of parenteral administration of Rp-8-Br-cAMPS in mice with MAIDS. We show that the compound is not toxic and partially restores the ex vivo proliferative responses to anti-CD3 mAb, but that it has no effect on the lymphadenopathy and splenomegaly characterizing the MAIDS syndrome.