Regulatory T cells for tolerance

Kawai, Kento; Uchiyama, Masateru; Hester, Joanna; Wood, Kathryn J.; Issa, Fadi

doi:10.1016/j.humimm.2017.12.013

Cited by 83 publications

(56 citation statements)

References 124 publications

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“…Treg constitute 3-10% of the naive peripheral CD4 + T cell pool in humans, are especially enriched in the CD4 + CD25 high population, may express the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, i.e., CD152), constitutively express the intracellular transcription factor FoxP3, and express low levels of CD127 low (IL-7 receptor) [3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Increased frequency of CD4⁺CD25^highCD127^lowT cells early after lung transplant is associated with improved graft survival – a retrospective study

et al. 2020

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In this retrospective study, we analyzed the presence of any association of three CD4 + CD25 high regulatory T-cell subpopulations at 3 weeks after lung transplantation with the later incidence of chronic lung allograft dysfunction and graft survival. Among lung-transplanted patients between January 2009 and April 2018, only patients with sufficient T-cell measurements at 3 weeks after transplantation were included into the study. Putative regulatory T cells were defined as CD4 + CD25 high T cells, detected in peripheral blood and further analyzed for CD127 low , FoxP3 + , and CD152 + using fluorescence-activated cell sorting (FACS) analysis. Associations of regulatory T cells with chronic lung allograft dysfunction (CLAD) and graft survival were evaluated using Cox analysis. During the study period, 724 (71%) patients were included into the study. Freedom from chronic lung allograft dysfunction (CLAD) and graft survival amounted to 66% and 68% at 5 years. At the multivariable analysis, increasing frequencies of CD127 low were associated with better freedom from CLAD (hazard ratio for each 1% increase of %CD127 low , HR = 0.989, 95% CI = 0.981-0.996, P = 0.003) and better graft survival (HR = 0.991, 95% CI = 0.984-0.999, P = 0.026). A higher frequency of CD127 low regulatory T cells in peripheral blood early after lung transplantation estimated a protective effect against chronic lung allograft dysfunction, mortality, and re-transplantation.

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Section: Introductionmentioning

confidence: 99%

Increased frequency of CD4⁺CD25^highCD127^lowT cells early after lung transplant is associated with improved graft survival – a retrospective study

et al. 2020

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“…The role of regulatory T cells (Tregs) in transplant tolerance has recently attracted great interest because tolerance was associated with accumulation of Tregs in the lymphoid tissues and transplanted organs . Therapeutic effects for ex vivo ‐expanded Tregs have been reported in murine models, in which their adoptive transfer facilitated the establishment of mixed chimerism, resulting in promotion of engraftment .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the impact of conventional immunosuppressant on the establishment of murine transplantation tolerance – an experimental study

et al. 2019

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Summary Regulatory T cells (Tregs) play a significant role in immune tolerance. Since Treg function deeply depends on Interleukin‐2 signaling, calcineurin inhibitors could affect their suppressive potentials, whereas mammalian target of rapamycin (mTOR) inhibitors may have less impact, as mTOR signaling is not fundamental to Treg proliferation. We previously reported a novel mixed hematopoietic chimerism induction regimen that promotes Treg proliferation by stimulating invariant natural killer T cells under CD40 blockade. Here, we use a mouse model to show the impact of tacrolimus (TAC) or everolimus (EVL) on the establishment of chimerism and Treg proliferation in the regimen. In the immunosuppressive drug‐dosing phase, peripheral blood chimerism was comparably enhanced by both TAC and EVL. After dosing was discontinued, TAC‐treated mice showed gradual graft rejection, whereas EVL‐treated mice sustained long‐term robust chimerism. Tregs of TAC‐treated mice showed lower expression of both Ki67 and cytotoxic T lymphocyte antigen‐4 (CTLA‐4), and lower suppressive activity in vitro than those of EVL‐treated mice, indicating that TAC negatively impacted the regimen by interfering with Treg proliferation and activation. Our results suggest that the usage of calcineurin inhibitors should be avoided if utilizing the regimen to induce Tregs in vivo for the establishment of mixed hematopoietic chimerism.

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“…For example, Tim‐3 has been associated with a shift in the balance from Th17 and Treg cells to Treg dominance . Moreover, PD‐1 and CTLA‐4 are critical in the suppressive activity of Treg cells, while PD‐1 + Tim‐3 + Treg cells exhibit higher effector function . HTR8/SVneo cells, as well as primary trophoblasts but not decidual stromal cells (data not shown) or OVC1 (an ovarian cancer cell line), up‐regulated CTLA‐4, Tim‐3, and PD‐1 expression in Treg cells along with TGF‐β1 production, indicating that fetal‐derived trophoblasts were pivotal inducers of maternal immune adaptation.…”

Section: Discussionmentioning

confidence: 94%

Bidirectional regulation between 1st trimester HTR8/SVneo trophoblast cells and in vitro differentiated Th17/Treg cells suggest a fetal‐maternal regulatory loop in human pregnancy

Wang

Qian

Sun

et al. 2019

American J Rep Immunol

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Problem During normal pregnancy, delicate crosstalk is established between fetus‐derived trophoblasts and maternal immune cells to ensure maternal‐fetal tolerance and successful placentation. Dysfunction in these interactions has been highly linked to certain pregnancy complications. Method of study Naïve CD4+T cells were cultivated with or without 1st trimester derived trophoblast cell line HTR8/SVneo cells in the absence or presence of T helper 17 (Th17) or regulatory (Treg)cell‐inducing differentiation conditions. After 5 days of co‐culture, HTR8/SVneo cells and CD4+T cells were harvested and analyzed using flow cytometry. Results CD4+T cells exposed to HTR8/SVneo cells showed enhanced induction of CD4+Foxp3+Treg cells with strong expression of TGF‐β1 and inhibitory molecules (cytotoxic T lymphocyte‐associated protein‐4 [CTLA‐4], T‐cell immunoglobulin mucin‐3 [Tim‐3], and programmed cell death‐1 [PD‐1]). Though not effecting Th17 differentiation, exposure to HTR8/SVneo cells promoted increased expression of proliferative and apoptotic markers on Th17 cells. Co‐culture with Th0 cells, or differentiated Th17 or Treg cells, down‐regulated Caspase‐3 and MMP‐9 (but not MMP‐2) expression in HTR8/SVneo cells, while promoting Ki67 expression. Conclusions HTR8/SVneo cells regulated maternal CD4+T‐cell differentiation, resulting in the expansion of immunosuppressive Treg cells, while CD4+T cells might promote the growth, and control the invasiveness of HTR8/SVneo cells. Thus, a bidirectional regulatory loop might exist between trophoblasts and maternal immune cell subsets, thereby promoting harmonious maternal‐fetal crosstalk.

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Regulatory T cells for tolerance

Cited by 83 publications

References 124 publications

Increased frequency of CD4⁺CD25^highCD127^lowT cells early after lung transplant is associated with improved graft survival – a retrospective study

Increased frequency of CD4⁺CD25^highCD127^lowT cells early after lung transplant is associated with improved graft survival – a retrospective study

Evaluation of the impact of conventional immunosuppressant on the establishment of murine transplantation tolerance – an experimental study

Bidirectional regulation between 1st trimester HTR8/SVneo trophoblast cells and in vitro differentiated Th17/Treg cells suggest a fetal‐maternal regulatory loop in human pregnancy

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Regulatory T cells for tolerance

Cited by 83 publications

References 124 publications

Increased frequency of CD4+CD25highCD127lowT cells early after lung transplant is associated with improved graft survival – a retrospective study

Increased frequency of CD4+CD25highCD127lowT cells early after lung transplant is associated with improved graft survival – a retrospective study

Evaluation of the impact of conventional immunosuppressant on the establishment of murine transplantation tolerance – an experimental study

Bidirectional regulation between 1st trimester HTR8/SVneo trophoblast cells and in vitro differentiated Th17/Treg cells suggest a fetal‐maternal regulatory loop in human pregnancy

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Increased frequency of CD4⁺CD25^highCD127^lowT cells early after lung transplant is associated with improved graft survival – a retrospective study

Increased frequency of CD4⁺CD25^highCD127^lowT cells early after lung transplant is associated with improved graft survival – a retrospective study