Mechanisms of T regulatory cell function

Askenasy, Nadir; Kaminitz, Ayelet; Yarkoni, Shai

doi:10.1016/j.autrev.2008.03.001

Cited by 154 publications

(127 citation statements)

References 40 publications

Supporting

Mentioning

118

Contrasting

Unclassified

Order By: Relevance

“…However, the data presented here vary from the absence of compensatory expansion of CD25 − FOXP3 + T cells in response to anti-CD25 antibodies in a model of experimental autoimmune encephalomyelitis in wild-type mice [38]. Since anti-CD25 antibodies do not always deplete CD25 + T cells [27], but rather inhibit their function [37], the cytokine environment might be less favourable for expansion of the CD25 − FOXP3 + T cells [39]. Reactive changes in CD25, CD62L and FOXP3 as phenotypic markers of putative Treg have been previously observed with immunomodulatory agents such as Cy, anti-IL-2, anti-CD25 and anti-CD3, and have been generally associated with positive outcome of immunomodulation in NOD mice [4,5,16,28].…”

Section: Discussionmentioning

confidence: 84%

Targeting of IL-2 receptor with a caspase fusion protein disrupts autoimmunity in prediabetic and diabetic NOD mice

Yarkoni¹,

Kaminitz

Sagiv³

et al. 2009

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis Interruption of IL-2 signalling is an attractive therapeutic target in autoimmune disorders. In this study we evaluated the effect of a fusion protein composed of IL-2 and caspase-3 (IL2-cas) on NOD mice, as compared with disease induction by cyclophosphamide. Methods IL2-cas was assessed in NOD mice at various ages and in conjunction with cyclophosphamide administration. The effect of IL2-cas on diabetogenic cells was evaluated in adoptive transfer experiments and in cell suspension in vitro. Results IL2-cas induced apoptosis in T cells expressing the α chain of the IL-2 receptor (cluster of differentiation [CD] 25) in vitro, with superior survival of T cells expressing CD4 and forkhead box P3 (FOXP3). The fusion protein decreased mixed lymphocyte reactivity, and pretreatment with IL2-cas decreased the efficacy of adoptive transfer of diabetes into NOD severe combined immunodeficiency mice. Administration of one dose of IL2-cas decreased the incidence of diabetes in NOD mice, showing a superior beneficial effect when administered at young age, and effectively blocked induction of hyperglycaemia by cyclophosphamide, reducing the severity of islet inflammation. Administration of IL2-cas caused an acute increase in CD25 -FOXP3 + T cells in the lymph nodes, pancreas and thymus in NOD mice, with similar effects in wild-type mice. Administration of IL2-cas after onset of hyperglycaemia resulted in superior survival. Conclusions/interpretation Targeted elimination of cells expressing the IL-2 receptor by this fusion protein disrupts the autoimmune pathogenesis in prediabetic and diabetic NOD mice, despite depletion of CD25 + regulatory T cells. Furthermore, this particular fusion protein is permissive to the development of FOXP3 + T cells that might contribute to protracted protection from the progression of insulitis and overt hyperglycaemia.

show abstract

Section: Discussionmentioning

confidence: 84%

Targeting of IL-2 receptor with a caspase fusion protein disrupts autoimmunity in prediabetic and diabetic NOD mice

Yarkoni¹,

Kaminitz

Sagiv³

et al. 2009

Diabetologia

View full text Add to dashboard Cite

show abstract

“…Treg cells modulate the immune response through three primary mechanisms: (i) the direct killing of cytotoxic cells through cell-to-cell contact; (ii) the inhibition of cytokine production by cytotoxic cells, in particular IL-2; and (iii) the direct secretion of immunomodulatory cytokines, such as TGFb and IL-10. 26 In this study, we investigated whether Treg cells affect OC formation and functional bone resorption and how such effects may occur. Our results showed that Treg cells inhibit the differentiation of OCs from BMCs in addition to the bone resorption of mature OCs.…”

Section: Modulation Of Treg Cells On Osteoclast Functionsmentioning

confidence: 99%

Estrogen enhances the functions of CD4+CD25+Foxp3+ regulatory T cells that suppress osteoclast differentiation and bone resorption in vitro

et al. 2010

View full text Add to dashboard Cite

Cross-talk has been shown to occur between the immune system and bone metabolism pathways. In the present study, we investigated the impact of CD4 1 CD25 1 Foxp3 1 regulatory T (Treg) cells on osteoclastogenesis and bone resorption. Treg cells that were isolated and purified from peripheral blood mononuclear cells (PBMCs) of healthy adults inhibited both the differentiation of osteoclasts (OCs) from human embryo bone marrow cells (BMCs) and the pit formation in a dose-dependent manner. In cell cocultures, the production levels of both interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-b1) were proportionally upregulated as the ratio of Treg cells to BMCs was increased, and the inhibition of OC differentiation and bone resorption by Treg cells was completely reversed by anti-IL-10 and anti-TGF-b1 antibodies. Treatment of BMC and Treg cell cocultures with 17b-estradiol (E2) at concentrations between 10 27 and 10 29 mol/l suppressed OC differentiation and bone resorption more efficiently than it did in cultures of BMCs alone; this enhanced suppression occurred via the stimulation of Treg cell IL-10 and TGF-b1 expression. These data suggest that Treg cells suppress OC differentiation and bone resorption by secreting IL-10 and TGF-b1. E2 enhances the suppressive effects of Treg cells on OC differentiation and bone resorption by stimulating IL-10 and TGF-b1 secretion from these cells. Therefore, Treg cell-derived IL-10 and TGF-b1 are likely involved in the regulation of E2 on bone metabolism and represent potential therapeutic targets for the treatment of postmenopausal osteoporosis (PMO).

show abstract

“…It is also under investigation what role (if any) probiotics have on T regulatory cells. 115,116 There are indications that the composition of commensal bacteria differs between children who develop atopic diseases and those who do not, and between children from countries with a high or low incidence of atopic disease. 117 However, to date, the differences identifi ed are not consistent between studies.…”

Section: Probiotics In Allergic Diseasesmentioning

confidence: 99%

Probiotics and immunity

et al. 2009

View full text Add to dashboard Cite

Probiotics are defi ned as live microorganisms that, when administered in adequate amounts, confer a health benefi t on the host, including the gastrointestinal tract. While this benefi cial effect was originally thought to stem from improvements in the intestinal microbial balance, there is now substantial evidence that probiotics can also provide benefi ts by modulating immune functions. In animal models, probiotic supplementation is able to provide protection from spontaneous and chemically induced colitis by downregulating infl ammatory cytokines or inducing regulatory mechanisms in a strain-specifi c manner. In animal models of allergen sensitization and murine models of asthma and allergic rhinitis, orally administered probiotics can straindependently decrease allergen-specifi c IgE production, in part by modulating systemic cytokine production. Certain probiotics have been shown to decrease airway hyperresponsiveness and infl ammation by inducing regulatory mechanisms. Promising results have been obtained with probiotics in the treatment of human infl ammatory diseases of the intestine and in the prevention and treatment of atopic eczema in neonates and infants. However, the fi ndings are too variable to allow fi rm conclusions as to the effectiveness of specifi c probiotics in these conditions.

show abstract

Mechanisms of T regulatory cell function

Cited by 154 publications

References 40 publications

Targeting of IL-2 receptor with a caspase fusion protein disrupts autoimmunity in prediabetic and diabetic NOD mice

Targeting of IL-2 receptor with a caspase fusion protein disrupts autoimmunity in prediabetic and diabetic NOD mice

Estrogen enhances the functions of CD4+CD25+Foxp3+ regulatory T cells that suppress osteoclast differentiation and bone resorption in vitro

Probiotics and immunity

Contact Info

Product

Resources

About