Regulatory T Cells and Transplantation Tolerance

Jiang, Shuiping; Lechler, Robert I.; He, Xiao Shun; Huang, Jie

doi:10.1016/j.humimm.2006.07.013

Cited by 80 publications

(70 citation statements)

References 146 publications

(139 reference statements)

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“…The study of Tregs has helped to highlight the importance of peripheral mechanisms in counteracting alloreactivity, modulating T-cell responses, and ultimately in the prevention of GvHD or autoimmunity (Asano et al, 1996;Jiang et al, 2006). For example, recent investigations have demonstrated that both the FoxP3+ and DN Tregs prevent GvHD in the murine system, and both possess in vitro suppressive activity in humans (Graca et al, 2002;Chen et al, 2004;Fischer et al, 2005;Hess, 2006;Jiang et al, 2006). To date, only the FoxP3 Tregs have been demonstrated to inversely correlate with (A) (B) n = 29 P < ·001 n = 29 P < ·001 GvHD in humans (Hess, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, peripheral tolerance mechanisms play an important role in inducing immunological acceptance of the allograft (Le & Chao, 2007). Investigations into the mechanisms of peripheral tolerance has led to the discovery of various subpopulations of regulatory T cells (Tregs) (Asano et al, 1996;Jiang et al, 2006) including (Palathumpat et al, 1992;Zhang et al, 2000), which have been studied in the present report.…”

mentioning

confidence: 87%

“…While the FoxP3 Tregs appear to be recent thymic emigrants (Jiang et al, 2006;Rezvani et al, 2006), DN Tregs arise in the periphery from chronically stimulated CD4 + T cells (Palathumpat et al, 1992;Yamagiwa et al, 1998;Ford et al, 2006;Zhang et al, 2007). Both populations can induce transplant tolerance (Chen et al, 2004), and expansion prior to HSCT prevents the development of GvHD in the murine model (Young et al, 2003;Joffre et al, 2004).…”

mentioning

confidence: 99%

“…Both populations can induce transplant tolerance (Chen et al, 2004), and expansion prior to HSCT prevents the development of GvHD in the murine model (Young et al, 2003;Joffre et al, 2004). Additionally, they both possess in vitro suppressive activity in humans (Joffre et al, 2004;Jiang et al, 2006). In contrast to FoxP3 Tregs, DN Tregs have the ability to acquire alloantigens from antigen-presenting cells, and present them to alloreactive syngeneic effector T cells in human in vitro studies.…”

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confidence: 99%

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Double‐negative regulatory T cells induce allotolerance when expanded after allogeneic haematopoietic stem cell transplantation

McIver¹,

Serio²,

Dunbar³

et al. 2008

Br J Haematol

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SummaryDouble-negative (DN) regulatory T cells (Tregs) are specialized T lymphocytes involved in the down-modulation of immune responses, resulting in allotolerance after allogeneic haematopoietic stem cell transplantation (HSCT). Most of the properties of DN Tregs were identified in murine models, including the unique ability to suppress alloreactive syngeneic effector T cells in an antigen-specific manner via Fas/ Fas-ligand interactions. We investigated the behaviour of DN Tregs following human allogeneic HSCT with regard to occurrence of graft-versus-host disease (GvHD) and restoration of T-cell receptor repertoire in a cohort of 40 patients. The frequency of DN Tregs and CD4/CD8 TCR repertoire was measured serially and at the time of diagnosis of GvHD by flow cytometry. Analysis demonstrated a positive correlation between degree of alloreactivity, as measured by grade of GvHD, and the number of variable beta chain (Vb) family expansions in both T-cell populations. We also found that a deficiency of DN Tregs was associated with an increased number of Vb family expansions, and most importantly, with the occurrence of GvHD. All individuals who demonstrated more than 1% DN Tregs did not develop GvHD, providing evidence that DN Tregs participate in peripheral tolerance to prevent GvHD when expanded after allogeneic HSCT.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 87%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Double‐negative regulatory T cells induce allotolerance when expanded after allogeneic haematopoietic stem cell transplantation

McIver¹,

Serio²,

Dunbar³

et al. 2008

Br J Haematol

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“…This suppression depends both on cell-contacts and on immunosuppressive cytokines such as TGF-ß and IL-10. Therefore, they are key regulators in the control of autoimmunity [2,33]. Intrathymic T-cell differentiation is supported by interaction between thymocytes and various components of the thymic microenvironment including TEC, macrophages, dendritic cells, fibroblasts, and extracellular matrix components [26,34].…”

Section: Cortexmentioning

confidence: 99%

Impact of the Somatotrope Growth Hormone (GH)/Insulin-Like Growth Factor 1 (IGF-1) Axis Upon Thymus Function: Pharmacological Implications in Regeneration of Immune Functions

Goffinet¹,

Mottet²,

Kermani³

et al. 2011

IEMAMC

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Abstract:The thymus is the central lymphoid structure where T-cell differentiation takes place, and a crucial organ for the maintenance of homeostasis in the immune system. Thymopoiesis includes intrathymic proliferation of T-cell precursors, selection and output of both self-tolerant and competent effector T cells, as well as of natural regulatory T cells (nTreg). In the crosstalk between the neuroendocrine and immune systems, peptide hormones have been more and more implicated in immunomodulation for the last thirty years. The somatotrope growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in particular has been repeatedly shown to play a major regulatory role upon thymus function and T-cell development. This review will focus on the important thymotropic properties of the somatotrope GH/IGF-1 axis, and will try to discriminate these properties in function of the endocrine or paracrine/autocrine pathways involved in their mediation. Most importantly, in light of an increasing number of recent studies, GH and IGF-1 now appear as novel therapeutic agents that could be used for enhancing thymopoiesis in different cases of immune deficiencies, including aging-related immune dysfunction.Keywords: Thymus, growth hormone (GH), insulin-like growth factors (IGFs), HIV, growth hormone deficiency (GHD), Chagas disease. GENERAL INTRODUCTIONThe thymus is now considered as a crucial organ for maintenance of immune system homeostasis and the central lymphoid organ where occurs the generation of self-tolerant and competent naive T cells, as well as self-antigen specific natural Treg cells [1,2]. However, for a long time, the thymus has been regarded as an endocrine gland. In addition, the thymus now appears as a privileged site where the endocrine and immune systems intimately interact.A permanent crosstalk exists between the neuroendocrine and immune systems [3][4][5][6]. In addition to the strong modulation of immunity by glucocorticoids and sexual steroids, other hormones have been more and more involved in immunomodulation. Indeed, the somatotrope GH/IGF-1 axis, as well as prolactin and thyroid hormones [7], were shown to play an important regulatory role in T-cell development [8][9][10].GH is mainly synthesised in the anterior pituitary gland but can also be produced by immune cells [11,12]. GH has several biological actions in the immune system including regulation of thymopoiesis and T-cell development [13]. Nevertheless, it is uneasy to distinguish whether the thymotropic effects of GH are direct or mediated by IGF-1, as most *Address correspondence to this author at the University of Liege Center of Immunoendocrinology (CIL), Institute of Pathology CHU-B23, B-4000 Liege-Sart Tilman, Belgium; Tel: +32 43 66 25 50; Fax: +32 43 66 98 59; E-mail: vgeenen@ulg.ac.be of GH effects are driven by induction of IGF-1 and as IGF-1 has also been described as an endogenous factor in the thymic microenvironment [12]. The evolution of the research field has brought new insights that justify an overview update as some ancie...

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