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00925njm 22002777a 4500 dc Rodriguez-Barbosa, Jose-Ignacio author Schneider, Pascal author Graca, Luis author Bühler, Leo author Perez-Simon, Jose-Antonio author Del Rio, Maria-Luisa author 2020-05-09 Regulatory T cells (Tregs) are essential for the maintenance of tolerance to self and non-self through cell-intrinsic and cell-extrinsic mechanisms. Peripheral Tregs survival and clonal expansion largely depend on IL-2 and access to co-stimulatory signals such as CD28. Engagement of tumor necrosis factor receptor (TNFR) superfamily members, in particular TNFR2 and DR3, contribute to promote peripheral Tregs expansion and sustain their survival. This property can be leveraged to enhance tolerance to allogeneic transplants by tipping the balance of Tregs over conventional T cells during the course of immune reconstitution. This is of particular interest in peri-transplant tolerance induction protocols in which T cell depletion is applied to reduce the frequency of alloreactive T cells or in conditioning regimens that allow allogeneic bone marrow transplantation. These conditioning regimens are being implemented to limit long-term side effects of continuous immunosuppression and facilitate the establishment of a state of donor-specific tolerance. Lymphopenia-induced homeostatic proliferation in response to cytoreductive conditioning is a window of opportunity to enhance preferential expansion of Tregs during homeostatic proliferation that can be potentiated by agonist stimulation of TNFR. http://hdl.handle.net/10668/15549 https://hdl.handle.net/20.500.12105/25267 32397343 10.3390/ijms21093347 1422-0067 International journal of molecular sciences TNF/TNF receptors Graft rejection Graft-versus-host disease Homeostatic proliferation Lymphopenia Regulatory T cells Transplantation The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens.