Recombinant IL-7/HGFβ efficiently induces transplantable murine hematopoietic stem cells

Lai, Laijun; Zhang, Mingfeng; Goldschneider, Irving

doi:10.1172/jci46055

Cited by 23 publications

(18 citation statements)

References 57 publications

(75 reference statements)

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“…The enhanced recovery of thymic cellularity was also noted in young and aged male as well as female mice. Lai and colleagues, using a mouse model of allogeneic BM transplantation, demonstrated the efficacy of a recombinant hybrid cytokine of IL-7 and hepatocyte growth factorβ (IL-7/HGFβ) to increase thymic reconstitution and functional activities of peripheral T cells (Jin et al 2011; Lai et al 2013). These studies provide important insights into potential MCM to stimulate regeneration of functional thymopoiesis.…”

Section: Discussionmentioning

confidence: 99%

Lymphoid and Myeloid Recovery in Rhesus Macaques Following Total Body X-Irradiation

Farese

Hankey

Cohen³

et al. 2015

Health Physics

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Recovery from severe immunosuppression requires hematopoietic stem cell reconstitution and effective thymopoiesis to restore a functional immune cell repertoire. Herein, a model of immune cell reconstitution consequent to potentially lethal doses of irradiation is described which may be valuable in evaluating potential medical countermeasures. Male rhesus macaques were total body irradiated by exposure to 6.00 Gy 250 kVp x-radiation (midline tissue dose, 0.13 Gy min-1) resulting in an approximate LD10/60 (n = 5/59). Animals received medical management and hematopoietic and immune cell recovery was assessed (n ≤ 14) through 370 days post exposure. A subset of animals (n ≤ 8) was examined through 700 days. Myeloid recovery was assessed by neutrophil and platelet-related parameters. Lymphoid recovery was assessed by the absolute lymphocyte count and FACS-based phenotyping of B- and T-cell subsets. Recent thymic emigrants were identified by T cell receptor excision circle quantification. Severe neutropenia, lymphopenia and thrombocytopenia resolved within 30 days. Total CD3+ cells μL-1 required 60 days to reach values 60% of normal, followed by subsequent slow recovery to approximately normal by 180 days post irradiation. Recovery of CD3+4+ and CD3+8+ cell memory and naïve subsets were markedly different. Memory populations were ≥ 100% of normal by day 60; whereas, naïve populations were only 57% normal at 180 days and never fully recovered to baseline post irradiation. Total (CD20+) B cells μL-1 were within normal levels by 77 days post exposure. This animal model elucidates the variable T- and B-cell subset recovery kinetics after a potentially lethal dose of total-body irradiation that are dependent on marrow-derived stem and progenitor cell recovery, peripheral homeostatic expansion and thymopoiesis.

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Section: Discussionmentioning

confidence: 99%

Lymphoid and Myeloid Recovery in Rhesus Macaques Following Total Body X-Irradiation

Farese

Hankey

Cohen³

et al. 2015

Health Physics

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“…Single cell suspensions of thymocytes and splenic cells were stained with fluorochrome‐conjugated antibodies as described . For intracellular staining, the cells were first permeabilized with a BD Cytofix/Cytoperm solution for 20 min at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Targeted deletion of c‐Met in thymic epithelial cells leads to an autoimmune phenotype

Song

et al. 2017

Immunol Cell Biol

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Hepatocyte growth factor (HGF) and its receptor c-Met signaling have been implicated in regulating various types of cells including epithelial cells. We have previously reported that c-Met is expressed by thymic epithelial cells (TECs), and that in vivo administration of hybrid cytokines containing IL-7 and the beta- or alpha-chain of HGF significantly increase the number of TECs. In order to study the role of c-Met signaling in TECs, we generated conditional knockout (cKO) mice in which c-Met was specifically deleted in TECs using a Foxn1-Cre transgene. We show here that c-Met deficiency in TECs results in age-progressive reduction in TEC number and reduced number of regulatory T cells. Consequently, c-Met TEC cKO mice displayed an autoimmune phenotype. Thus, c-Met signaling in TECs is important for the maintenance of TECs and immune self-tolerance.

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“…The single-cell suspension was stained with fluorochrome-conjugated antibodies directly or indirectly as described [14]. For intracellular staining, the cells were first permeabilized with a BD Cytofix/Cytoperm solution for 20 minutes at 4°C.…”

Section: Methodsmentioning

confidence: 99%

ESC-derived thymic epithelial cells expressing MOG prevents EAE by central and peripheral tolerance mechanisms

Lin

Cui

et al. 2017

Cellular Immunology

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Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis (MS), and is induced by immunization with disease-causative self-antigens such as myelin oligodendrocyte glycoprotein (MOG). We have previously reported that transplantation of MOG expressing thymic epithelial progenitors (TEPs) derived from 129S6SvEv Tac mouse embryonic stem cells (mESCs) prevented the development of EAE. In this study, we expand our previous studies to show that transplantation of MOG expressing mESC-TEPs derived from C57BL/6 mice also prevents EAE development. Furthermore, by using a MOG-specific T cell receptor (TCR) transgenic mouse model, we demonstrate that both central and peripheral tolerances are involved in the prevention of EAE induced by MOG expressing mESC-TEPs. Our results suggest that transplantation of human ESC-TEPs expressing MOG may provide an effective approach for the induction of MOG-specific immune tolerance, thereby the prevention and treatment of MS.

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Recombinant IL-7/HGFβ efficiently induces transplantable murine hematopoietic stem cells

Cited by 23 publications

References 57 publications

Lymphoid and Myeloid Recovery in Rhesus Macaques Following Total Body X-Irradiation

Lymphoid and Myeloid Recovery in Rhesus Macaques Following Total Body X-Irradiation

Targeted deletion of c‐Met in thymic epithelial cells leads to an autoimmune phenotype

ESC-derived thymic epithelial cells expressing MOG prevents EAE by central and peripheral tolerance mechanisms

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