Conversion of CD73hiFR4hi anergic T cells to IFN-γ–producing effector cells disrupts established immune tolerance

Dangi, Anil; Husain, Irma; Jordan, Collin Z.; Yu, Shuangjin; Luo, Xunrong

doi:10.1172/jci163872

Cited by 4 publications

(3 citation statements)

References 5 publications

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“…Cytomegalovirus infection breaks established tolerance in a model of murine islet allotransplantation, 81 a mechanism that appears dependent on the conversion of anergic T cells to IFN-γproducing effector T cells. 82 Other similar models of tolerance using donor-specific transfusion have shown that disruption of tolerance also occurs with Toll-like receptor engagement after CpG (5-cytosine-phosphate-guanine-3) oligonucleotide administration. 83 NHPs are valuable preclinical models for transplant immunology research, with highly conserved MHC proteins between NHP and humans.…”

Section: Efficacy Of Apoptotic Donor Cells In Animal Modelsmentioning

confidence: 99%

Negative Vaccination Strategies for Promotion of Transplant Tolerance

Tunbridge,

Luo,

Thomson

2024

Transplantation

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Organ transplantation requires the use of immunosuppressive medications that lack antigen specificity, have many adverse side effects, and fail to induce immunological tolerance to the graft. The safe induction of tolerance to allogeneic tissue without compromising host responses to infection or enhancing the risk of malignant disease is a major goal in transplantation. One promising approach to achieve this goal is based on the concept of “negative vaccination.” Vaccination (or actively acquired immunity) involves the presentation of both a foreign antigen and immunostimulatory adjuvant to the immune system to induce antigen-specific immunity. By contrast, negative vaccination, in the context of transplantation, involves the delivery of donor antigen before or after transplantation, together with a “negative adjuvant” to selectively inhibit the alloimmune response. This review will explore established and emerging negative vaccination strategies for promotion of organ or pancreatic islet transplant tolerance. These include donor regulatory myeloid cell infusion, which has progressed to early-phase clinical trials, apoptotic donor cell infusion that has advanced to nonhuman primate models, and novel nanoparticle antigen-delivery systems.

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Section: Efficacy Of Apoptotic Donor Cells In Animal Modelsmentioning

confidence: 99%

Negative Vaccination Strategies for Promotion of Transplant Tolerance

Tunbridge,

Luo,

Thomson

2024

Transplantation

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“…It has not been fully determined whether differences in TCR signaling affect the induction of CD4 + T cell anergy. However, it has been suggested that low-affinity TCR interaction with pMHC can induce anergy, resulting in CD4 + T cells that lack the capacity to proliferate or produce IL-2 [ 14 ]. Alteration of the timing of the TCR-pMHC interaction can also lead to CD4 + T cell anergy, for example, a short-duration TCR-pMHC interaction or low TCR signaling [ 14 , 15 ].…”

Section: Anergymentioning

confidence: 99%

“…However, it has been suggested that low-affinity TCR interaction with pMHC can induce anergy, resulting in CD4 + T cells that lack the capacity to proliferate or produce IL-2 [ 14 ]. Alteration of the timing of the TCR-pMHC interaction can also lead to CD4 + T cell anergy, for example, a short-duration TCR-pMHC interaction or low TCR signaling [ 14 , 15 ]. Overall, the identification of anergic CD4 + T cells in humans has been challenging, especially considering the lack of distinct markers.…”

Section: Anergymentioning

confidence: 99%

Immunological mechanisms of tolerance: Central, peripheral and the role of T and B cells

Meng,

Layhadi,

Keane

et al. 2023

Asia Pacific Allergy

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T and B cells are key components of the adaptive immune system. Through their immune properties and their interactions with other immune cells and cytokines around them, they build a complex network to achieve immune tolerance and maintain homeostasis of the body. This is achieved through mechanisms of central and peripheral tolerance, both of which are associated with advantages and disadvantages. For this reason, the immune system is tightly regulated and their dysregulation can result in the subsequent initiation of various diseases. In this review, we will summarize the roles played by T cells and B cells within immune tolerance with specific examples in the context of different diseases that include allergic disease. In addition, we will also provide an overview on their suitability as biomarkers of allergen-specific immunotherapy.

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