Augmented Induction of CD4+CD25+ Treg using Monoclonal Antibodies to CD200R

Gorczynski, Reginald M.; Lee, Lydia; Boudakov, Ivo

doi:10.1097/01.tp.0000152118.51622.f9

Cited by 112 publications

(92 citation statements)

References 25 publications

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“…CD200 is thought to induce Tregs that inhibit the immune response of tumor-specific effector T-cells [22]. In contrast, Treg levels in the present study were not correlated with CD200-expressing T-cells in the present study.…”

Section: Erçetin Et Al T Regulatory Cells In Multiple Myelomacontrasting

confidence: 55%

The correlation between T regulatory cells and autologous peripheral blood stem cell transplantation in multiple myeloma

Ercetin

Aktaş²,

Pişkin³

et al. 2011

Turk J Hematol

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Objective: Multiple myeloma (MM) is characterized by malignant proliferation of plasmocytes and their precursors. T regulatory cells (Tregs) have a role in immunosuppression and control of autoimmunity, and are currently an important topic in the study of immune response to tumor cells. The correlation between Tregs and autologous peripheral blood stem cell transplantation (APBSCT) in MM has not been studied. The aim of this study was to compare CD4+CD25+FOXP3+ Treg, CD200, and PD-1 levels in MM patients that did and did not undergo APBSCT. Materials and Methods: Peripheral blood samples were collected from 28 MM patients ranging in age from 41 to 78 years for analysis of CD4CD25+ FOXP3+ Tregs, PD-1 (CD279), and CD200. Peripheral blood mononuclear cells were isolated via density gradient centrifugation. Four-color flow cytometry was performed. Using a sequential gating strategy, Tregs were identified as CD4+CD25+FOXP3+ T-cells. Results were analyzed using the Mann Whitney U non-parametric test and a compare means test. p values <0.05 were considered statistically significant. Results: The study included 28 MM patients (10 female and 18 male). In all, 11 of the patients underwent APBSCT. The level of Tregs identified as CD4+CD25+FOXP3+ T-cells was higher in the patients that underwent APBSCT (p=0.042). CD200 and PD-1 levels did not significantly differ between the 2 groups (p=0.711 and p=0.404, respectively). There weren't any statistically significant differences in CD200, PD-1, or CD4+CD25+FOXP3+ T-cell levels between the patients that did and did not undergo APBSCT (p>0.05). Conclusion: Treg levels were higher in the patients that underwent APBSCT. Tregs are crucial for the induction and maintenance of peripheral tolerance to self-antigens. In addition, Tregs can suppress immune responses to tumor antigens; however, APBSCT and Treg levels were not correlated with CD200 or PD-1 expression. Relationship of Tregs with prognosis needs to be determined by studies that include larger cohorts. (Turk J Hematol 2011; 28: 107-14)

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Section: Erçetin Et Al T Regulatory Cells In Multiple Myelomacontrasting

confidence: 55%

The correlation between T regulatory cells and autologous peripheral blood stem cell transplantation in multiple myeloma

Ercetin

Aktaş²,

Pişkin³

et al. 2011

Turk J Hematol

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“…As reported in earlier publications, as judged by neutralization of functional activity by anti-TGF-␤ and/or anti-IL-10 (see legend to Fig. 1), these Foxp3 ϩ Treg were dependent upon expression of TGF-␤ (and IL-10) for function (11,29).…”

Section: Both Cd200fc and Anti-cd200r2 Mab 4b9 Polarizes Bmdcs From Cmentioning

confidence: 51%

“…In contrast, CD200 interacting with alternate CD200R isoforms expressed at the cell surface of myeloid-derived cells fails to produce direct immunosuppression in similar assays (8), and distinct biochemical signaling pathways have been reported to be activated following interaction of CD200 with different CD200R family members (9,10). Triggering of alternate CD200R isoforms seems to be instrumental in directing differentiation of bone marrow precursors in vitro into dendritic cell (DC) 3 populations that are able in turn to induce development of CD4 ϩ CD25 ϩ Foxp3 ϩ regulatory T cells (Treg) with immunoregulatory properties in a mouse transplant model (skin graft rejection) (11).…”

mentioning

confidence: 99%

An Interaction between CD200 and Monoclonal Antibody Agonists to CD200R2 in Development of Dendritic Cells That Preferentially Induce Populations of CD4+CD25+ T Regulatory Cells

Gorczynski

Khatri

Lee

et al. 2008

The Journal of Immunology

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In previous studies we reported that while interaction between the relatively ubiquitously expressed molecule CD200 and one of its receptors, CD200R1, resulted in direct suppression of alloreactivity, engagement of alternate receptors led instead to altered differentiation of dendritic cells (DCs) from marrow precursors, which could in turn foster development of Foxp3+ regulatory T cells. We have explored this effect of engagement of alternate receptors by using a monoclonal agonist Ab to CD200R2 and investigating expression of TLRs on DCs induced in vivo and in vitro after CD200 stimulation in mice in which the gene encoding CD200R1 was deleted. CD200 stimulation was achieved by using either a soluble form of CD200 (CD200Fc) or overexpression of CD200 as a doxycycline-inducible transgene. Although broadly similar effects were seen, consistent with the hypothesis that triggering of CD200R2 does produce DCs with a characteristic TLR repertoire, there are subtle differences in suppression of alloreactivity achieved by CD200 delivered in these two manners, which is consistent with a complexity of CD200:CD200R engagement not previously appreciated.

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“…The suggestion from our data that CD200 is acting indirectly is intriguing. CD200 acting on immature DC has been reported to promote development of tolerance and Treg cells (that appear to act by a short-range cell contact mechanism) [11,[13][14][15]. Indeed, in a mouse model of ITP, it was also not possible to show a role for cytokines in the beneficial effects of IVIG treatment [16].…”

Section: Discussionmentioning

confidence: 99%

“…CD200 is a tolerance signaling molecule expressed on a variety of cells including activated T and B cells, brain cells, and fetal trophoblasts, and acts by binding to CD200 receptors [8,9]. This binding results in generation of different types of immunoregulatory suppressor T cells, including CD4 + 25 + Treg cells, and activation of indoleamine 2,3-dioxygenase production in myeloid cells [10,11]. When murine or human lymphocytic cells are stored at 4°C overnight, cell surface CD200 is lost and activity blocking anti-CD200 binding to fresh cells is present in conditioned supernatant [7].…”

Section: Introductionmentioning

confidence: 99%

CD200-dependent and nonCD200-dependant pathways of NK cell suppression by human IVIG

Clark

Wong

Banwatt

et al. 2008

J Assist Reprod Genet

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Augmented Induction of CD4+CD25+ Treg using Monoclonal Antibodies to CD200R

Abstract: Unlike anti-CD200R1, anti-CD200R2 both promotes development of DCs with capacity to induce Treg and directly augments thymocyte production of Treg.

Cited by 112 publications

References 25 publications

The correlation between T regulatory cells and autologous peripheral blood stem cell transplantation in multiple myeloma

The correlation between T regulatory cells and autologous peripheral blood stem cell transplantation in multiple myeloma

An Interaction between CD200 and Monoclonal Antibody Agonists to CD200R2 in Development of Dendritic Cells That Preferentially Induce Populations of CD4+CD25+ T Regulatory Cells

CD200-dependent and nonCD200-dependant pathways of NK cell suppression by human IVIG

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