Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients

Banerjee, Devi; Dhodapkar, Madhav V.; Matayeva, Elyana; Steinman, Ralph M.; Dhodapkar, Kavita M.

doi:10.1182/blood-2006-03-011353

Cited by 270 publications

(254 citation statements)

References 39 publications

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“…This is surprising given the low amounts of IL-12p70 released from cocktailmatured DC in vitro but may be explained by their expression of CD70 [20,54]. The vaccine-specific Th cells were FOXP3-negative, indicating that vaccine-specific natural Treg were not induced, which is counterintuitive to a previous report [55], yet compatible with recent Treg cloning data [56]. Vaccine-specific CTL were, however, only weakly detectable ex vivo, but the CTLp frequency was markedly increased, and many CTL were of high affinity.…”

Section: Modc As a Focus For Comparisoncontrasting

confidence: 76%

Dendritic cells in cancer immunotherapy

Schuler

2010

Eur J Immunol

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DC initiate and regulate T‐cell immunity and are thus the key to optimization of all types of vaccines. Insights into DC biology offer many opportunities to enhance immunogenicity. In this Viewpoint, I discuss some recent developments and findings that are of immediate relevance for the clinical development of cancer vaccines. In addition, I emphasize my personal view that we should explore the potential of adoptively transferred DC (i.e. DC vaccination) as cancer vaccines by performing two‐armed trials that address critical variables and by delivering antigens via mRNA‐transfected DC.

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Section: Modc As a Focus For Comparisoncontrasting

confidence: 76%

Dendritic cells in cancer immunotherapy

Schuler

2010

Eur J Immunol

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“…34 There is evidence in the literature that proliferation of Tregs induced by mature allogeneic or syngeneic DCs derived from bone marrow cells is dependent on exogenous IL-2. 33 In our experiments, exogenous IL-2 was not necessary for expansion of CD4 + CD25 + Foxp3 + cells.…”

Section: Discussionmentioning

confidence: 99%

Expansion of CD4⁺ CD25⁺ Foxp3⁺ T cells by bone marrow‐derived dendritic cells

et al. 2009

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Summary Dendritic cells (DCs) are the most important antigen‐presenting cells of the immune system and have a crucial role in T‐lymphocyte activation and adaptive immunity initiation. However, DCs have also been implicated in maintaining immunological tolerance. In this study, we evaluated changes in the CD4+ CD25+ Foxp3+ T‐cell population after co‐culture of lymph node cells from BALB/c mice with syngeneic bone marrow‐derived DCs. Our results showed an increase in CD4+ CD25+ Foxp3+ T cells after co‐culture which occurred regardless of the activation state of DCs and the presence of allogeneic apoptotic cells; however, it was greater when DCs were immature and were pulsed with the alloantigen. Interestingly, syngeneic apoptotic thymocytes were not as efficient as allogeneic apoptotic cells in expanding the CD4+ CD25+ Foxp3+ T‐cell population. In all experimental settings, DCs produced high amounts of transforming growth factor (TGF)‐β. The presence of allogeneic apoptotic cells induced interleukin (IL)‐2 production in immature and mature DC cultures. This cytokine was also detected in the supernatants under all experimental conditions and enhanced when immature DCs were pulsed with the alloantigen. CD4+ CD25+ Foxp3+ T‐cell expansion during co‐culture of lymph node cells with DCs strongly suggested that the presence of alloantigen enhanced the number of regulatory T cells (Tregs) in vitro. Our data also suggest a role for both TGF‐β and IL‐2 in the augmentation of the CD4+ CD25+ Foxp3+ population.

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“…Most studies have focused on dendritic cells (DC), which are thought to be key players in generating peripheral Treg [20][21][22]. B cells are also APC that present antigen to T cells.…”

Section: Introductionmentioning

confidence: 99%

Resting B cells expand a CD4⁺CD25⁺Foxp3⁺ Treg population via TGF‐β3

Shah

Qiao

2008

Eur J Immunol

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Regulatory T cells (Treg) play critical roles in maintaining tolerance and preventing autoimmunity. It is not fully clear how these cells are generated and maintained. Here, we show that resting B cells are able to expand Treg. This expansion requires TGF-b3 and signaling through the TCR and CD28. Upon activation, B cells express less TGF-b3, which reduces their capacity to expand Treg and which also results in increased Treg death. This may ensure that B cells can function as potent professional antigen presenting cells during infections. However, in the absence of any infection, we find that B-cell-deficient lMT mice have decreased percentages of Treg in the periphery. Our data suggest that resting B cells, which may be presenting self-antigens to T cells, can expand and maintain specific Treg and thus might be involved in the prevention of autoimmunity. Key words: B cells . Regulatory T cells . Tolerance Supporting Information available online IntroductionRegulatory T cells (Treg) are a subset of T cells that can actively suppress innate as well as adaptive immunity and have been implicated in self-tolerance, autoimmunity, cancer, transplantation immunology and a myriad of infectious diseases [1][2][3][4][5][6]. There are numerous different subsets of Treg based on their phenotypic markers, amonge which the naturally occurring Treg (nTreg) population is well studied and characterized. nTreg are a subset of CD4 1 T cells expressing CD25 and the transcription factor Forkhead box protein 3 (Foxp3). Foxp3 has been shown to be the master regulator for the generation of nTreg. Although Foxp3 À/À mice lack CD4 1 CD25 1 T cells, expression of Foxp3 in CD4 1 CD25 -T cells is sufficient for converting them into CD4 1 CD25 1 T cells with suppressive function [7,8].CD4 1 CD25 1 Foxp3 1 Treg arise in the thymus and enter into the periphery where they constitute $5-10% of the CD4 1 T cells. nTreg generation in the thymus is thought to require high-affinity peptide-MHC class II interactions in contrast to low-affinity peptide-MHC class II interactions required for positive selection of conventional CD4 1 T cells [9,10]. There are also strong evidences for the generation of CD4 1 CD25 1 Foxp3 1 Treg in the periphery. Experiments carried out in thymectomized or RAG-2-deficient mice lacking CD4 1 CD25 1 T cells show that nTreg can be generated in the periphery from CD4 1 CD25 À T cells [11,12].In addition to co-stimulation via the B7-CD28 and TCR-MHC class II pathways, various cytokines such as IL-2, TGF-b1 and IL-10 have been associated with the generation of peripheral Treg. IL-2 and IL-2R knockout mice have few, if any, nTreg and develop severe lymphoproliferation and autoimmunity [13,14]. TGF-b1 or IL-10 have been shown to expand Treg and even convert CD4 1 CD25 À T cells into CD4 1 CD25 1 T cells with suppressive functions [13,[15][16][17][18].Antigen presenting cells (APC) express both MHC class II as well as B7 molecules and secrete cytokines that may modulate the differentiation of T cells into either T-effector or T-r...

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Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients

Cited by 270 publications

References 39 publications

Dendritic cells in cancer immunotherapy

Dendritic cells in cancer immunotherapy

Expansion of CD4⁺ CD25⁺ Foxp3⁺ T cells by bone marrow‐derived dendritic cells

Resting B cells expand a CD4⁺CD25⁺Foxp3⁺ Treg population via TGF‐β3

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Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients

Cited by 270 publications

References 39 publications

Dendritic cells in cancer immunotherapy

Dendritic cells in cancer immunotherapy

Expansion of CD4+ CD25+ Foxp3+ T cells by bone marrow‐derived dendritic cells

Resting B cells expand a CD4+CD25+Foxp3+ Treg population via TGF‐β3

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Expansion of CD4⁺ CD25⁺ Foxp3⁺ T cells by bone marrow‐derived dendritic cells

Resting B cells expand a CD4⁺CD25⁺Foxp3⁺ Treg population via TGF‐β3