Antigen Specific Regulatory T Cells in Kidney Transplantation and Other Tolerance Settings

Hu, Min; Rogers, Natasha M.; Li, Jennifer; Zhang, Geoff Y.; Wang, Yuan Min; Shaw, Karli; O’Connell, Philip J.; Alexander, Stephen I.

doi:10.3389/fimmu.2021.717594

Cited by 19 publications

(26 citation statements)

References 130 publications

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“…However, it has been shown that the depletion of memory T cells in bone marrow transplants can cause an increase in graft failure and the recurrence of leukemias and tumors [ 69 , 70 ]. It has now been found in clinical transplant trials that Treg inoculation manipulated by blocking the costimulatory pathway B7-CD28 using CTLA-4 Ig/Fc) or/and CD40-CD40L (using anti- CD154 mAb) demonstrated improved tolerance to transplants and reduced the need for immunosuppression [ 71 ].…”

Section: Treg Cells and Transplantationmentioning

confidence: 99%

Ozone Pollution, Oxidative Stress, Regulatory T Cells and Antioxidants

et al. 2022

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Ozone pollution, is a serious health problem worldwide. Repeated exposure to low ozone doses causes a loss of regulation of the oxidation–reduction systems, and also induces a chronic state of oxidative stress. This fact is of special importance for the regulation of different systems including the immune system and the inflammatory response. In addition, the oxidation–reduction balance modulates the homeostasis of these and other complex systems such as metabolism, survival capacity, cell renewal, and brain repair, etc. Likewise, it has been widely demonstrated that in chronic degenerative diseases, an alteration in the oxide-reduction balance is present, and this alteration causes a chronic loss in the regulation of the immune response and the inflammatory process. This is because reactive oxygen species disrupt different signaling pathways. Such pathways are related to the role of regulatory T cells (Treg) in inflammation. This causes an increase in chronic deterioration in the degenerative disease over time. The objective of this review was to study the relationship between environmental ozone pollution, the chronic state of oxidative stress and its effect on Treg cells, which causes the loss of regulation in the inflammatory response as well as the role played by antioxidant systems in various pathologies.

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Section: Treg Cells and Transplantationmentioning

confidence: 99%

Ozone Pollution, Oxidative Stress, Regulatory T Cells and Antioxidants

et al. 2022

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“…Transplant tolerance has been achieved by infusion of CD4 + CD25 + Tregs or CD4 + Foxp3 + Tregs in a variety of animal models (106,107). CD4 + Foxp3 + Tregs have been studied as a potential therapeutic in human solid organ transplantation with the objective of minimizing the requirement for immunosuppression in transplantation (108)(109)(110)(111), and has been proposed as a potential therapeutic strategy in the islet xenotransplant setting (95).…”

Section: The Role Of Regulatory T Cells In T Cell Mediated Islet Xeno...mentioning

confidence: 99%

Cellular Immune Responses in Islet Xenograft Rejection

Hawthorne

et al. 2022

Front. Immunol.

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Porcine islets surviving the acute injury caused by humoral rejection and IBMIR will be subjected to cellular xenograft rejection, which is predominately mediated by CD4+ T cells and is characterised by significant infiltration of macrophages, B cells and T cells (CD4+ and CD8+). Overall, the response is different compared to the alloimmune response and more difficult to suppress. Activation of CD4+ T cells is both by direct and indirect antigen presentation. After activation they recruit macrophages and direct B cell responses. Although they are less important than CD4+ T cells in islet xenograft rejection, macrophages are believed to be a major effector cell in this response. Rodent studies have shown that xenoantigen-primed and CD4+ T cell-activated macrophages were capable of recognition and rejection of pancreatic islet xenografts, and they destroyed a graft via the secretion of various proinflammatory mediators, including TNF-α, reactive oxygen and nitrogen species, and complement factors. B cells are an important mediator of islet xenograft rejection via xenoantigen presentation, priming effector T cells and producing xenospecific antibodies. Depletion and/or inhibition of B cells combined with suppressing T cells has been suggested as a promising strategy for induction of xeno-donor-specific T- and B-cell tolerance in islet xenotransplantation. Thus, strategies that expand the influence of regulatory T cells and inhibit and/or reduce macrophage and B cell responses are required for use in combination with clinical applicable immunosuppressive agents to achieve effective suppression of the T cell-initiated xenograft response.

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“…Importantly, in vitro studies have shown that allospecific Tregs outperform polyclonal Tregs in suppressive capacity (26)(27)(28)(29)(30)(31)(32)(33), resulting in lower Treg cell numbers required. Allospecific Tregs can theoretically be generated through several methods including expansion through direct antigen presentation by donor APCs, indirect antigen presentation with patient APCs pulsed with peptide from donor or tetramers made up of patient HLA class II, as recently reviewed by Hu et al (34). As these methods are rather cumbersome and difficult to standardize, alternative means to achieve donor-specificity are warranted.…”

Section: Introductionmentioning

confidence: 99%

Chimeric Antigen Receptor (CAR) Regulatory T-Cells in Solid Organ Transplantation

et al. 2022

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Solid organ transplantation is the treatment of choice for various end-stage diseases, but requires the continuous need for immunosuppression to prevent allograft rejection. This comes with serious side effects including increased infection rates and development of malignancies. Thus, there is a clinical need to promote transplantation tolerance to prevent organ rejection with minimal or no immunosuppressive treatment. Polyclonal regulatory T-cells (Tregs) are a potential tool to induce transplantation tolerance, but lack specificity and therefore require administration of high doses. Redirecting Tregs towards mismatched donor HLA molecules by modifying these cells with chimeric antigen receptors (CAR) would render Tregs far more effective at preventing allograft rejection. Several studies on HLA-A2 specific CAR Tregs have demonstrated that these cells are highly antigen-specific and show a superior homing capacity to HLA-A2+ allografts compared to polyclonal Tregs. HLA-A2 CAR Tregs have been shown to prolong survival of HLA-A2+ allografts in several pre-clinical humanized mouse models. Although promising, concerns about safety and stability need to be addressed. In this review the current research, obstacles of CAR Treg therapy, and its potential future in solid organ transplantation will be discussed.

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Antigen Specific Regulatory T Cells in Kidney Transplantation and Other Tolerance Settings

Cited by 19 publications

References 130 publications

Ozone Pollution, Oxidative Stress, Regulatory T Cells and Antioxidants

Ozone Pollution, Oxidative Stress, Regulatory T Cells and Antioxidants

Cellular Immune Responses in Islet Xenograft Rejection

Chimeric Antigen Receptor (CAR) Regulatory T-Cells in Solid Organ Transplantation

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