Objectif
In developed countries, most HIV-infected patients are under highly active antiretroviral therapy (HAART). However, despite controlled viral replication, the immune reconstitution often remains incomplete, probably due to a poor reconstitution of thymic production. Apart its role in educating a diverse repertoire of conventional T-cells, the thymus also produces natural regulatory T-cells (nTreg), which contributes to the regulation of immune responses. Various cytokines are presently proposed as immunotherapy susceptible to help reconstituting circulating T-cell pool. Among these, Interleukin-7 is certainly the more promising as it directly affects thymic function, allowing T-cell neo-production and thus the enlargement of circulating T-cell repertoire diversity. The 3ITD project aims to a) analyze the physiology of nTreg production by the thymus; b) precisely evaluate the impact of acute SIV infection on nTreg production and identify the cytokines involved in early thymic defects; c) realize a pre-clinical study using recombinant IL-7 as a potential therapeutic to reconstitute nTreg subset in chronically HIV-infected patients and in HIV/HCV co-infected patients presenting with IFNα therapy-induced lymphopenia. The 3ITD project will be developed in 3 stages: a) definition of the phenotype of nTregs recently emigrated from the thymus; b) estimation of the impact of acute SIV infection and IFNα therapy; c) evaluation of the relevance of IL-7 treatment. The 3ITD project will provide a better understanding of the physiology of nTregs maturation by the thymus and of the modifications induced by HIV infection. Moreover, the 3ITD project will provide pre-clinical rationale for the use of IL-7 as a therapeutic compound in the treatment of virally- or pharmaceutically-induced nTreg deficiencies. It will impact the researcher’s growth and contribute to European excellence and knowledge transfer. Thus it is relevant to People specific, Capacity and Cooperation EC Program.
Champ scientifique
Thème(s)
Appel à propositions
FP7-PEOPLE-2009-IEF
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Régime de financement
MC-IEF - Intra-European Fellowships (IEF)Coordinateur
75654 Paris
France