FOXP3+ regulatory T cells: From suppression of rejection to induction of renal allograft tolerance

Dummer, Claus Dieter; Carpio, Virna Nowotny; Gonçalves, Luiz Felipe Santos; Manfro, Roberto Ceratti; Veronese, Francisco Veríssimo

doi:10.1016/j.trim.2011.08.009

Cited by 72 publications

(54 citation statements)

References 100 publications

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“…Multiple studies have demonstrated that Tregs promote postischemic kidney preconditioning and repair, suppress rejection, and induce allograft tolerance in kidney transplantation. [30][31][32][33] Alternately, DCs and macrophages have been shown to worsen ischemic injury through various mechanisms and depletion of these cells protects the kidney from IR injury. [34][35][36][37][38] Although numbers of DCs and macrophages increased after IR compared with baseline kidneys, their number was low in kidneys of CD4-Keap1-KO mice in this study.…”

Section: Discussionmentioning

confidence: 99%

T Lymphocyte–Specific Activation of Nrf2 Protects from AKI

Noel¹,

Martina

Bandapalle³

et al. 2015

Journal of the American Society of Nephrology

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T lymphocytes are established mediators of ischemia reperfusion (IR)-induced AKI, but traditional immune principles do not explain their mechanism of early action in the absence of alloantigen. Nrf2 is a transcription factor that is crucial for cytoprotective gene expression and is generally thought to have a key role in dampening IRinduced AKI through protective effects on epithelial cells. We proposed an alternative hypothesis that augmentation of Nrf2 in T cells is essential to mitigate oxidative stress during IR-induced AKI. We therefore generated mice with genetically amplified levels of Nrf2 specifically in T cells and examined the effect on antioxidant gene expression, T cell activation, cytokine production, and IR-induced AKI. T cell-specific augmentation of Nrf2 significantly increased baseline antioxidant gene expression. These mice had a high frequency of intrarenal CD25 increased T cell expression of Nrf2 were significantly protected from functional and histologic consequences of AKI. Furthermore, adoptive transfer of high-Nrf2 T cells protected wild-type mice from IR injury and significantly improved their survival. These data demonstrate that T cell-specific activation of Nrf2 protects from IR-induced AKI, revealing a novel mechanism of tissue protection during acute injury responses.

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Section: Discussionmentioning

confidence: 99%

T Lymphocyte–Specific Activation of Nrf2 Protects from AKI

Noel¹,

Martina

Bandapalle³

et al. 2015

Journal of the American Society of Nephrology

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“…33 Such association do not mean that Foxp3 + T-regs induce inflammation by themselves, but rather, it seems that they are regulatory cells, generated by the inflammatory process of rejection to stabilize the inflammation by lowering the activity of effector T cells in a timedependent manner to promote a state of transplant tolerance. 34 The role of Foxp3 + T-regs during graft rejection will be clearer if Foxp3 expression is normalized to the T-lymphocyte compartment that infiltrates the graft, and not the whole graft tissue sampling. Earlier approaches have considered Foxp3 expression as a contributory component of the lymphocyte infiltration, rather than an indicative of the extent of the inflammatory infiltrate.…”

Section: General Prospective Of Mechanisms Used By Regulatory T Cellsmentioning

confidence: 99%

Regulatory T Cells as a Therapeutic Tool To Induce Solid-Organ Transplant Tolerance: Current Clinical Experiences

Nikoueinejad¹,

Sharif²,

Amirzargar³

et al. 2013

Exp Clin Transplant

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Long-term tolerance is potentially an ideal in organ transplant. Achieving this leads us to eliminate immunosuppressive therapies and their associated side effects. Although most succession in this field belongs to mixed chimerism methods of tolerance induction, regulatory T cells and (T-reg)-based methods also have been demonstrated to prevent organ rejection and lead to transplant tolerance through different mechanisms. In contrast to chimeric protocols (which require bone marrow transplant), T-reg-mediated protocols do not aggressively manipulate blood and the immune system. Most treatment has been done for graft-versus-host disease after hematopoietic stem cell transplant. This review describes different types and mechanisms of action and clinical strategies using T-regs to induce transplant tolerance.

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“…During in vivo attempts with the mentioned antibodies, the best results of treatment of melanoma and other examined tumours proved to be obtained using parallel administration of both mentioned antibodies targeted at CTLA-4 (Ipilimumab) and PD-1 (Nivolumab), the action of which supplement each other [19,52,78]. Patients after chemotherapy or chemotherapy associated with immunotherapy with rytuximab following administration of the mentioned above drugs manifested for many months a slowed down tumour development.…”

Section: Description Of Principles In Tumour Treatment Taking Into Amentioning

confidence: 99%

Problems of Cancer Treatment. Part 2. Treatment Based on Modification of Anticancer Immunological Responses in Therapy

Kawiak

Hoser

Domagała‐Kulawik

2017

Advances in Cell Biology

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Summary:Here we present the concept of making own patient's anti-cancer treatment more efficient and starting at testing the efficacy of immunological system. The respective tests are suggested, with special attention devoted to tumour-induced microenvironmental changes. The tumour should be considered to represent a complex tissue in which the cancer cells communicate directly and indirectly with the surrounding cellular immunological surrounding and develope traits that promote their own survival. The results of tests allow to propose a rational, individually profiled treatment of a patient, especially directed to elimination of blocks inhibiting the immunological system due to effects of cancer cells. The elimination can be implemented using commercially available antibodies, targeted at the cell surface receptors for inhibitors of T lymphocytes (CTLA-4 and PD-1). Outcome of the therapy is slow to appear and the results used to be selective. Some patients gain long term improvement and respective predictive markers are now tested. It is assumed that the future anti-cancer therapy will be individually targeted, based on individual tests and an assistance of own immunological system of the cancer patient.

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FOXP3+ regulatory T cells: From suppression of rejection to induction of renal allograft tolerance

Cited by 72 publications

References 100 publications

T Lymphocyte–Specific Activation of Nrf2 Protects from AKI

T Lymphocyte–Specific Activation of Nrf2 Protects from AKI

Regulatory T Cells as a Therapeutic Tool To Induce Solid-Organ Transplant Tolerance: Current Clinical Experiences

Problems of Cancer Treatment. Part 2. Treatment Based on Modification of Anticancer Immunological Responses in Therapy

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