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Analysis of regulatory T cell proliferation and apoptosis in vivo at the cellular and molecular level

Final Report Summary - TREG (Analysis of regulatory T cell proliferation and apoptosis in vivo at the cellular and molecular level)

Progress towards objectives
- Aim 1. To characterise the cellular properties of Foxp3+ regulatory T cells in regards to homeostasis, proliferation and apoptosis (Period 1)
- Aim 2. To test the role of Bcl-2 family members in controlling the proliferative and apoptotic properties of Foxp3+ regulatory T cells (Period 2)
- Aim 3. To test the role of the Pdl / IL-2 axis in modulating Foxp3+ regulatory T cell numbers during inflammation (Period 2)

Description of work performed
- Foxp3DTR/Thy1.1 system setup and optimised
- Kinetics of regulatory T cell reconstitution measured
- Contribution of proliferation and apoptosis to regulatory T cell reconstitution measured
- Role of Bcl2, BclX, Mcl1 in regulatory T cell homeostasis assessed
- Role of Bim, Bak/Bad in regulatory T cell homeostasis assessed
- Role of dendritic cells, IL-2 and costimulation in regulatory T cell homeostasis assessed
- Construct and mice for IL2 over-expression generated

Description of main results
- Identification of Mcl1 as the primary factor for regulatory T cell homeostasis
- Determination that Bcl2 and BclX play little role in regulatory T cell homeostasis
- Identification of Bak/Bax as key regulators of regulatory T cell number
- Identification of Bim as key regulators of regulatory T cell number
- Identification of costimulation, but not dendritic cells, as key regulators of regulatory T cell homeostasis
- Identification of IL-2 effect on Mcl1 and survival
- Analysis of kinetics of regulatory T cell response to disturbed homeostasis

Potential impact
- Aid in the future design of therapeutics to alter regulatory T cell number. Patent submitted for gene-therapy use
- Eg identification of Mcl1 as key drug target. Patent submitted for gene-therapy use
- Development would have large impact on patients with autoimmune disease