Service Communautaire d'Information sur la Recherche et le Développement - CORDIS

Mechanisms of suppression of T cell responses by immunoregulatory cells

The partner provided data on functional activity of CD4+CD25+ T cells purified from post-natal human thymuses, the so-called Natural Treg Cells.

Their suppressive activity was contact-dependent and appeared to be related to their ability to down-regulate the IL-2 receptor (IL-2R) - chain expression in target T cells via the combined action of TGF-1 and CTLA-4 expressed on their membrane.

Moreover, both CD4+ Treg cells completely suppressed the proliferation of Th1 clones, but exhibited significantly lower suppressive activity on the proliferation of Th2 clones.

Another mechanism concerns Mesenchymal stem cells (MSC), which are progenitor cells with immunoregulatory properties. The anti-proliferative effect of MSC on T cells and NK cells requires the presence of IFN-gamma produced by activated T cells and NK cells. IFN-gamma acts by enhancing indoleamine 2,3-diooxygenase which induces kinurenines showing anti-proliferative and pro-apoptotic activities.

These findings allow defining some molecules as therapeutical targets to be associated with DNA vaccines in vitro or in vivo models.

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University of Firenze
Policlinico Careggi, Viale Morgagni, 85
50134 Firenze
Italy
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