"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."