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Roles of IL-7 in the regulation of T cell homeostasis

Objective

Interleukin-7 promotes survival and proliferation of lymphocytes both during thyrnic maturation and also in the case of mature peripheral cells. In HTV-infected individuals and in clinical settings, which result in T cell depletion an increase of serum, IL-7 concentration was found. Increased production of IL-7 in response to T cell loss is considered as a homeostatic response mechanism aiming at the restoration of peripheral T cell number. In our previous studies we found a decreased level of IL-7R in HIV-infected patients and the decrease of the receptor was correlated with the level of T cell depletion and also with the increase of serum IL-7 concentrations. These results suggest that low IL-7R expression of T cells may contribute to the loss of T lymphocytes in HIV-infected individuals and may also limit the positive effects of the high IL-7 concentration on T cells.

Our research objectives discussed in the proposal are the following:
1) Assay the hypothesis that low IL-7R expression of T lymphocytes in HIV positive subjects may result in survival disadvantage for peripheral T lymphocytes. Analyse if known apoptosis regulatory molecules are affected in 1L-7R negative T cells from HIV patients.
2) Analyse if dendritic cells (DC) can produce IL-7 and characterise those factors of DC maturation and activation, which regulate IL-7 expression. Test the hypothesis if DC can present IL-7 to T cells by binding the cytokine to the extracellular matrix with a similar mechanism described in the case of bone marrow stromal cells.
3) Analysis of the production and functon of the soluble IL-7Ra protein. We plan to screen which cells produce the soluble form of the IL-7R and analyse if the soluble receptor can interfere with the effects of IL-7.
4) Analyse if IL-7 plays a role in the regulation of HIV tropism.
Our research may open new lines of thinking in field of T cell homeostasis in HIV-infected individuals.

Call for proposal

FP6-2002-MOBILITY-5
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Funding Scheme

EIF - Marie Curie actions-Intra-European Fellowships

Coordinator

KAROLINSKA INSTITUTET
Address
Nobels Vaeg 1
Stockholm
Sweden