RESEARCH ARTICLE


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
1 Immunology and Infectious Diseases Laboratory, GIGA-Research, B34, University of Liége-CHU Liége, 4000 Liége,Belgium
2 Animal Facility, GIGA-Research, B23, University of Liége, 4000 Liége, Belgium
3 Department of Pathology, GIGA-Research, University of Liége-CHU Liège, 4000 Liége, Belgium
4 Biotechnology Centre of Oslo, University of Oslo, P.O. Box 1125, Blindern, 0317 Oslo, Norway and Lauras AS,Gaustadalléen 21, N-0349 Oslo, Norway


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© 2008 Nayjib et al.;

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.

* Address correspondence to this author at the Immunology and Infectious Diseases Laboratory, GIGA-Research, B34, University of Liège-CHU Liège, 4000 Liège, Belgium; Tel: +32 4366 2482; Fax: +32 4366 4534; E-mail: srahmouni@ulg.ac.be
§ These two authors contributed equally to this work.


Abstract

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.