Sujeong Jin

CAR19 Tregs treat murine chronic graft-versus-host disease through immune suppression without measurable B cell cytolysis

Sujeong Jin, Michael Zaiken, Cameron McDonald-Hyman, Christina R. Hartigan et autres

Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic transplantation. cGVHD pathophysiology involves cooperation between T follicular helper cells (TFHs) and germinal center B cells (GCBs), allo- and autoantibody depositions in cGVHD tissues, and fibrosis. We …

Human CD8-iTreg are potent GVHD suppressors and tumoricidal effectors by release of Granzyme-K + Supramolecular Attack Particles

Jemma H. Larson, Ewoud B. Compeer, Phillip R. Dougherty, Kyle Smith et autres

Abstract Regulatory CD8 + T-cells (CD8 + Treg) are a distinct yet understudied T-cell subset capable of simultaneous immunosuppression and cytolysis. Here, we characterized induced human CD8 + Treg (CD8-iTreg) generated from peripheral blood CD8 + CD25⁻ T-cells using anti-CD3e mAb-loaded artificial …

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Monocarboxylate transporter 1 deficient donor T cells rewire metabolism and ameliorate aGVHD lethality

Eun‐A Ko, Asim Saha, Cameron McDonald-Hyman, Sujeong Jin et autres

Abstract Introduction Allogeneic hematopoietic stem cell transplantation is limited by complications, including acute graft-versus-host disease (aGVHD). Donor graft naive T cells that are alloreactive differentiate into effector T cells, as key drivers of aGVHD, and produce proinflammatory cytokines and cytotoxic molecules. Alloreactive …

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Deficiency of T follicular helper cell Tet3 DNA demethylation inhibits pathogenic IgG2c class switching and chronic GVHD

Michael Zaiken, Sujeong Jin, Cameron McDonald-Hyman, Christina R. Hartigan et autres

ABSTRACT: Chronic graft-versus-host disease (cGVHD) is the leading cause of morbidity and nonrelapse-associated mortality after allogeneic hematopoietic cell transplantation. Treating steroid resistant/refractory cGVHD remains challenging. Epigenetic regulators can have global transcriptional effects that control donor T-cell responses. We previously showed that inhibiting …

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Human CAR19 CD8+ iTreg exceed CAR19 CD8 CTLs both in suppressing GVHD lethality and eliminating CD19+ Nalm-6 lymphoma cells in vivo

Jemma H. Larson, Ewoud B. Compeer, Mehrdad Hefazi, Kyle D. Smith et autres

Abstract Simultaneously achieving a graft versus leukemia (GVL) effect while suppressing graft versus host disease (GVHD) would facilitate the development of immunotherapies for hematopoietic stem cell transplantation. Here, we show that human peripheral blood CD8+CD25− T-cells cultured with IL-2, TGF-β and rapamycin …

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Enforced gut homing of murine regulatory T cells reduces early graft-versus-host disease severity

Jemma H. Larson, Sujeong Jin, Michaël Loschi, Sara Bolivar-Wagers et autres

Damage to the gastrointestinal tract following allogeneic hematopoietic stem cell transplantation is a significant contributor to the severity and perpetuation of graft-versus-host disease. In preclinical models and clinical trials, we showed that infusing high numbers of regulatory T cells reduces graft-versus-host disease …

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Prevention of acute GVHD using an orthogonal IL-2/IL-2Rβ system to selectively expand regulatory T cells in vivo

Teresa Lopes Ramos, Sara Bolivar-Wagers, Sujeong Jin, Govindarajan Thangavelu et autres

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for patients with hematological disorders and bone marrow (BM) failure syndromes. Graft-versus-host disease (GVHD) remains a leading cause of morbidity posttransplant. Regulatory T cell (Treg) therapies are efficacious in ameliorating GVHD but …

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Murine CAR19 Tregs suppress acute graft-versus-host disease and maintain graft-versus-tumor responses

Sara Bolivar-Wagers, Michaël Loschi, Sujeong Jin, Govindarajan Thangavelu et autres

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) efficacy is complicated by graft-versus-host disease (GVHD), a leading cause of morbidity and mortality. Regulatory T cells (Tregs) have shown efficacy in preventing GVHD. However, high Treg doses are often required, necessitating substantial ex vivo or …

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Retinoic acid signaling acts as a rheostat to balance Treg function

Govindarajan Thangavelu, Gabriela Andrejeva, Sara Bolivar-Wagers, Sujeong Jin et autres

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Augmenting oxidation of branched-chain amino acids (BCAAs) treats murine chronic Graft-Versus-Host Disease (cGVHD)

Sujeong Jin, Sara Bolivar-Wagers, Kirsti L. Walker, Emily T. Mirek et autres

Abstract Aberrant immune responses, such as high Tfollicular helper (Tfh) and germinal center B cells (GCB) in cGVHD inducing antibody (Ab) secretion with tissue deposition and fibrosis, require distinct metabolic reprogramming to sustain pathogenesis. Leucine, isoleucine, and valine are essential BCAAs that …

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Cytolytic CD4+ and CD8+ Regulatory T-Cells and Implications for Developing Immunotherapies to Combat Graft-Versus-Host Disease

Sara Bolivar-Wagers, Jemma H. Larson, Sujeong Jin, Bruce R. Blazar

Regulatory T-cells (Treg) are critical for the maintenance of immune homeostasis and tolerance induction. While the immunosuppressive mechanisms of Treg have been extensively investigated for decades, the mechanisms responsible for Treg cytotoxicity and their therapeutic potential in regulating immune responses have been …

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BET-bromodomain and EZH2 inhibitor–treated chronic GVHD mice have blunted germinal centers with distinct transcriptomes

Michael Zaiken, Ryan Flynn, Katelyn Paz, Stephanie Y. Rhee et autres

Despite advances in the field, chronic graft-versus-host-disease (cGVHD) remains a leading cause of morbidity and mortality following allogenic hematopoietic stem cell transplant. Because treatment options remain limited, we tested efficacy of anticancer, chromatin-modifying enzyme inhibitors in a clinically relevant murine model of …

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