Dendritic cells with TGF-β1 differentiate naïve CD4+CD25−T cells into islet-protective Foxp3+regulatory T cells

Luo, Xunrong; Tarbell, Kristin V.; Yang, Hua; Pothoven, Kathryn L.; Bailey, Samantha; Ding, Ruchuang; Steinman, Ralph M.; Suthanthiran, Manikkam

doi:10.1073/pnas.0611646104

Cited by 214 publications

(184 citation statements)

References 38 publications

Supporting

Mentioning

169

Contrasting

Unclassified

Order By: Relevance

“…DC can differentiate T regs in the thymus [78] and in the periphery [79], and expand them once the T regs have formed [80][81][82]. Antigen-specific T regs are much more effective than polyclonal populations in suppressing immunity in vivo [79,[81][82][83]. For many years, the major approach to the induction of peripheral tolerance has been to inject very large doses of antigen.…”

Section: Tolerogenicity Another Side Of Immunogenicitymentioning

confidence: 99%

Dendritic cells: Understanding immunogenicity

2007

View full text Add to dashboard Cite

The impetus for the discovery of dendritic cells in 1972 was to understand immunogenicity, the capacity of an antigenic substance to provoke immunity. During experiments to characterize "accessory" cells that enhanced immunity, we spotted unusual stellate cells in mouse spleen. They had a distinct capacity to form and retract processes or dendrites and were named dendritic cells (DC). DC proved to be different from other cell types and to be peculiarly immunogenic when loaded with antigens. When Langerhans cells were studied, immunogenicity was found to involve two steps: antigen presentation by immature DC and maturation to elicit immunity. Antigenbearing DC were also immunogenic in vivo and were therefore termed "nature's adjuvants". Several labs then learned to generate large numbers of DC from progenitors, which accelerated DC research. Tolerogenicity via DC, including the control of foxp3 + suppressor T cells, was recently discovered. Two areas of current research that I find intriguing are to identify mechanisms for antigen uptake and processing, and for the control of different types of immunity and tolerance. These subjects should be studied in vivo with clinically relevant antigens, so that the activities of DC can be better integrated into the prevention and treatment of disease in patients.

show abstract

Section: Tolerogenicity Another Side Of Immunogenicitymentioning

confidence: 99%

Dendritic cells: Understanding immunogenicity

2007

View full text Add to dashboard Cite

show abstract

“…Mice lacking Stat3 in myeloid compartment of tumor stroma, including DCs and macrophages, showed reduced numbers of tumor-infiltrating CD4 + CD25 + /Foxp3 + /Lag-3 + Tregs, which was accompanied by increased CD8 + effector T cells. An important role of TGFβ in mediating Treg expansion through direct interaction of CD4 + CD25 + cells with DCs has been demonstrated in various systems [20,21]. In addition, resident tumor DCs might also actively promote immunosuppression through expansion of Tregs [22].…”

Section: Role Of Stat3 In Regulatory T Cellsmentioning

confidence: 99%

Role of Stat3 in suppressing anti-tumor immunity

Kortylewski

2008

Current Opinion in Immunology

168

119

View full text Add to dashboard Cite

Recent evidence suggests that what sustains a tumor's survival and proliferation can also subvert the immune system from its defense role. As a point of convergence for numerous oncogenic signaling pathways, Stat3 is constitutively activated in diverse human cancer cells. Activated Stat3 not only upregulates genes critical for survival, proliferation, angiogenesis and metastasis, it also promotes expression of immune suppressive factors while inhibiting Th1 immunostimulatory molecules. By virtue of its ability to promote expression of many factors that activate Stat3 in diverse cells, Stat3 allows malignant and immune cells resonate, forming close partnership for tumor immune evasion, tumor progression and resistance to therapies.

show abstract

“…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

View full text Add to dashboard Cite

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...

show abstract

Dendritic cells with TGF-β1 differentiate naïve CD4⁺CD25⁻T cells into islet-protective Foxp3⁺regulatory T cells

Cited by 214 publications

References 38 publications

Dendritic cells: Understanding immunogenicity

Dendritic cells: Understanding immunogenicity

Role of Stat3 in suppressing anti-tumor immunity

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

Contact Info

Product

Resources

About

Dendritic cells with TGF-β1 differentiate naïve CD4+CD25−T cells into islet-protective Foxp3+regulatory T cells

Cited by 214 publications

References 38 publications

Dendritic cells: Understanding immunogenicity

Dendritic cells: Understanding immunogenicity

Role of Stat3 in suppressing anti-tumor immunity

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

Contact Info

Product

Resources

About

Dendritic cells with TGF-β1 differentiate naïve CD4⁺CD25⁻T cells into islet-protective Foxp3⁺regulatory T cells

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