Human FOXP3+ Regulatory T Cells in Transplantation

Boros, Péter; Bromberg, Jonathan S.

doi:10.1111/j.1600-6143.2009.02704.x

Cited by 40 publications

(39 citation statements)

References 35 publications

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“…Recent studies indicate that regulatory T cells (Tregs) play an important role in the suppression of autoimmunity and induction of immunological tolerance after organ transplantation (Tx) [1,2,3,4,5]. Although several types of Tregs exist, the best characterized population of Tregs in humans co-express the CD4 and CD25 (IL-2 receptor α chain, p55) surface antigens [1,2,3].…”

Section: Introductionmentioning

confidence: 99%

“…Although several types of Tregs exist, the best characterized population of Tregs in humans co-express the CD4 and CD25 (IL-2 receptor α chain, p55) surface antigens [1,2,3]. Tregs also have low or negative expression of the CD127 surface molecule [6].…”

Section: Introductionmentioning

confidence: 99%

“…Tregs also have low or negative expression of the CD127 surface molecule [6]. Natural Tregs (nTregs) arise in the thymus and express the transcription factor FoxP3 that controls Treg development and function and is considered as their most specific marker [1,2,3]. Tregs also arise in the periphery (inducible Tregs, iTregs) from naive CD4 T cells when they are stimulated by certain types of antigen (self or alloantigen or oral antigen), in the presence of certain cytokines (mainly IL-4, IL-10, TGF-β and IL-17).…”

Section: Introductionmentioning

confidence: 99%

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Different Immunosuppressive Combinations on T-Cell Regulation in Renal Transplant Recipients

et al. 2010

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Background/Aims: Recent studies indicate that regulatory T-cells (Tregs) promote transplant tolerance. We studied Treg levels in 39 stable renal transplant recipients to determine the sizes of the Treg populations and the effects of treatment regimens thereof. Methods: All patients (19 with good graft function and 20 with chronic allograft nephropathy) received induction therapy (basiliximab) and were on triple immunosuppressive regimens with calcineurin inhibitors (cyclosporine or tacrolimus), mycophenolate mofetil (MMF) or everolimus and steroids. Twenty healthy subjects served as controls. Whole blood samples were stained with anti-CD4, CD25, CD127, and FoxP3 antibodies and analyzed by flow cytometry to determine CD4+CD25^highFoxP3± and CD4+ CD25^highCD127^–/low Treg levels. Results:All patients had significantly reduced CD4+CD25^highFoxP3± but no CD4+ CD25^highCD127^–/low Treg levels compared to controls. Renal allograft function did not correlate with Treg levels. Statistically significant correlations between CD4+CD25^highFoxp3+ Tregs and tacrolimus levels and CD4+CD25^highFoxp3– Tregs and HLA-DR mismatching were detected. Patients receiving MMF had significantly higher CD4+CD25^highFoxp3+ Tregs compared to patients on everolimus who were also receiving lower doses of calcineurin inhibitors. Conclusion:Overall, immunosuppression lowers CD4+CD25^highFoxP3± Treg levels significantly in the periphery in renal transplant recipients. In addition, different immunosuppressive regimens have different impacts on CD4+CD25^highFoxP3+ Tregs, a fact that may influence long-term allograft survival.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Different Immunosuppressive Combinations on T-Cell Regulation in Renal Transplant Recipients

et al. 2010

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“…Par ailleurs, d'autres travaux rapportent un taux de Treg significativement bas dans le sang de patients ayant un rejet chronique de greffe de foie. Ainsi, le résultat de la greffe (tolérance ou rejet) dépend probablement de la balance entre Teff allogéniques et Treg [17].…”

Section: Dans La Transplantation D'organeunclassified

Actualité sur les lymphocytes T régulateurs CD4⁺

2012

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“…Theoretically, one could consider T reg induction in the treatment of autoimmunity (Kim et al, 2007), to establish tolerance to a transplanted organ (Boros and Bromberg, 2009), or in the treatment of spontaneous abortions (Leber et al, 2010). In this case, potential side effects could include increased risk of infection or cancer associated with impaired immunosurveillance.…”

Section: Implications Of T Reg Therapy In the Treatment Of Immunologimentioning

confidence: 99%

Safety assessment of immunomodulatory biologics: The promise and challenges of regulatory T-cell modulation

Ponce

2011

Journal of Immunotoxicology

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Regulatory T-cell (T reg ) modulation is developing as an important therapeutic opportunity for the treatment of a number of important diseases, including cancer, autoimmunity, infection, and organ transplant rejection. However, as demonstrated with IL-2 and TGN-1412, our understanding of the complex immunological interactions that occur with T reg modulation in both non-clinical models and in patients remains limited and appears highly contextual. This lack of understanding will challenge our ability to identify the patient population who might derive the highest benefit from T reg modulation and creates special challenges as we transition these therapeutics from non-clinical models into humans. Thus, in vivo testing in the most representative animal model systems, with careful progress in the clinic, will remain critical in developing therapeutics targeting T reg and understanding their clinical utility. Moreover, toxicology models can inform some of the potential liabilities associated with T reg modulation, but not all, suggesting a continued need to explore and validate predictive models.

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Human FOXP3+ Regulatory T Cells in Transplantation

Cited by 40 publications

References 35 publications

Different Immunosuppressive Combinations on T-Cell Regulation in Renal Transplant Recipients

Different Immunosuppressive Combinations on T-Cell Regulation in Renal Transplant Recipients

Actualité sur les lymphocytes T régulateurs CD4⁺

Safety assessment of immunomodulatory biologics: The promise and challenges of regulatory T-cell modulation

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Human FOXP3+ Regulatory T Cells in Transplantation

Cited by 40 publications

References 35 publications

Different Immunosuppressive Combinations on T-Cell Regulation in Renal Transplant Recipients

Different Immunosuppressive Combinations on T-Cell Regulation in Renal Transplant Recipients

Actualité sur les lymphocytes T régulateurs CD4+

Safety assessment of immunomodulatory biologics: The promise and challenges of regulatory T-cell modulation

Contact Info

Product

Resources

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Actualité sur les lymphocytes T régulateurs CD4⁺