Regulatory T Cells and Immune Tolerance

Sakaguchi, Shimon; Yamaguchi, Tomoyuki; Nomura, Takashi; Ono, M.

doi:10.1016/j.cell.2008.05.009

Cited by 4,253 publications

(3,736 citation statements)

References 118 publications

Supporting

Mentioning

3,614

Contrasting

Unclassified

Order By: Relevance

“…They are therefore crucial for the maintenance of immune self‐tolerance and homeostasis (for review, see Sakaguchi et al ., 2008). The most studied Treg cells are the CD4 + CD25 hi FoxP3 + that are required for self‐tolerance and a proper immune response to pathogens (Sakaguchi, 2005).…”

Section: Cellular Senescence and Immunity In Tissue Homeostasismentioning

confidence: 99%

Cellular senescence impact on immune cell fate and function

et al. 2016

View full text Add to dashboard Cite

SummaryCellular senescence occurs not only in cultured fibroblasts, but also in undifferentiated and specialized cells from various tissues of all ages, in vitro and in vivo. Here, we review recent findings on the role of cellular senescence in immune cell fate decisions in macrophage polarization, natural killer cell phenotype, and following T‐lymphocyte activation. We also introduce the involvement of the onset of cellular senescence in some immune responses including T‐helper lymphocyte‐dependent tissue homeostatic functions and T‐regulatory cell‐dependent suppressive mechanisms. Altogether, these data propose that cellular senescence plays a wide‐reaching role as a homeostatic orchestrator.

show abstract

Section: Cellular Senescence and Immunity In Tissue Homeostasismentioning

confidence: 99%

Cellular senescence impact on immune cell fate and function

et al. 2016

View full text Add to dashboard Cite

show abstract

“…CD4 + cells expressing the transcription factor FoxP3 and high levels of CD25 play an important role in the maintenance of self‐tolerance and immune homeostasis, and the absence of FoxP3 expression results in susceptibility to development of autoimmunity, immunopathology, and lymphoproliferative disease (reviewed in 216, 225). Naive CD4 + T cells expressing FoxP3 are produced by the thymus.…”

Section: Regulatory Cell Populations and Their Relationship To Bnab Imentioning

confidence: 99%

“…Naive CD4 + T cells expressing FoxP3 are produced by the thymus. These cells, which are termed natural CD4 + Treg cells (nTregs) (reviewed in 225), respond to antigenic stimulation by differentiating into effector Treg cells 226. There are nTreg cells with specificity for both self and foreign antigens, although the ratio of antigen‐specific FoxP3 + to FoxP3 − cells is higher for the former, enabling more stringent control of responses to autoantigens 227.…”

Section: Regulatory Cell Populations and Their Relationship To Bnab Imentioning

confidence: 99%

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Borrow

Moody

2017

Immunological Reviews

View full text Add to dashboard Cite

SummaryInduction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV‐1) is a key, as‐yet‐unachieved goal of prophylactic HIV‐1 vaccine strategies. However, some HIV‐infected individuals develop bnAbs after approximately 2‐4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+ T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+ (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy‐chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+ Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV‐1 infection, in particular alterations in CD4+ Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV‐1 vaccine design.

show abstract

“…CD4ϩCD25ϩ Treg cells can be generated peripherally from CD4ϩCD25Ϫ T cells (2,29). To determine whether the human AD-MSC-induced increase in CD4ϩCD25ϩ Treg cells during CIA was due to expansion of the existing, naturally occurring CD4ϩCD25ϩ Treg cells or to Treg cells newly generated from CD4ϩCD25Ϫ T cells, mice with CIA were depleted of CD4ϩCD25ϩ T cells before injection with human ADMSCs.…”

Section: Immune Tolerance Induction With Human Ad-mscs In Experimentamentioning

confidence: 99%

“…On the other hand, failures in the function of the Treg cell compartment can contribute to the development of RA, and enhancing the function of this compartment may also represent a therapeutic strategy (2)(3)(4)(5)(6).…”

mentioning

confidence: 99%

Treatment of experimental arthritis by inducing immune tolerance with human adipose‐derived mesenchymal stem cells

González¹,

González‐Rey²,

Rico³

et al. 2009

Arthritis & Rheumatism

447

357

View full text Add to dashboard Cite

Objective. Rheumatoid arthritis (RA) is a chronic autoimmune disease caused by loss of immunologic self tolerance and characterized by chronic joint inflammation. Adult mesenchymal stem cells (MSCs) were recently found to suppress effector T cell responses and to have beneficial effects in various immune disorders. The purpose of this study was to examine a new therapeutic strategy for RA based on the administration of human adipose-derived MSCs (AD-MSCs).Methods. DBA/1 mice with collagen-induced arthritis were treated with human AD-MSCs after disease onset, and clinical scores were determined. Inflammatory response was determined by measuring the levels of different mediators of inflammation in the joints and serum. The Th1-mediated autoreactive response was evaluated by determining the proliferative response and cytokine profile of draining lymph node cells stimulated with the autoantigen. The number of Treg cells and the suppressive capacity on self-reactive Th1 cells were also determined.Results. Systemic infusion of human AD-MSCs significantly reduced the incidence and severity of experimental arthritis. This therapeutic effect was mediated by down-regulating the 2 deleterious disease components: the Th1-driven autoimmune and inflammatory responses. Human AD-MSCs decreased the production of various inflammatory cytokines and chemokines, decreased antigen-specific Th1/Th17 cell expansion, and induced the production of antiinflammatory interleukin-10 in lymph nodes and joints. Human ADMSCs also induced de novo generation of antigenspecific CD4؉CD25؉FoxP3؉ Treg cells with the capacity to suppress self-reactive T effector responses.Conclusion. Human AD-MSCs emerge as key regulators of immune tolerance by inducing the generation/activation of Treg cells and are thus attractive candidates for a cell-based therapy for RA.

show abstract

Regulatory T Cells and Immune Tolerance

Cited by 4,253 publications

References 118 publications

Cellular senescence impact on immune cell fate and function

Cellular senescence impact on immune cell fate and function

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Treatment of experimental arthritis by inducing immune tolerance with human adipose‐derived mesenchymal stem cells

Contact Info

Product

Resources

About