A nomogram based on clinicopathological and ultrasound characteristics to predict central neck lymph node metastases in papillary thyroid cancer.

Purpose: Papillary thyroid cancer (PTC) has grown rapidly in prevalence over the past few decades, and central neck lymph node metastasis (CNLNM) is associated with poor prognoses. However, whether to carry out preventive central neck lymph node dissection (CNLND) is still controversial. We aimed to construct a prediction model of CNLNM to facilitate making clinical surgical regimens.

Association of the Coronavirus Disease 2019 Outbreak on the Diabetes Self-Management in Chinese Patients: An Analytical Cross-Sectional Study.

Background: The coronavirus disease 2019 (COVID-19) outbreak has seriously affected people's lives, especially those with chronic diseases. Diabetes self-management, which plays an important role in glycaemic control and reducing the risk of acute and long-term complications, may be discouraged by social distancing.

Purpose: To evaluate the level of self-management activities in Chinese patients with type 2 diabetes mellitus (T2DM) during the COVID-19 pandemic.

CD4(+) T-cell subsets in transplantation.

The identification of T-helper 9 (Th9), Th17, Th22 cells as distinct subsets of CD4(+) T cells has extended the Th1/Th2 paradigm in the adaptive immunity. In the past decade, many studies in animal models and clinical transplantation have demonstrated that interleukin-17 (IL-17) is involved in allograft rejection. It appears that Th17 cells together with Th1 and Th2 cells play an important role in mediating allograft rejection.

T cell signaling targets for enhancing regulatory or effector function.

To respond to infection, resting or naïve T cells must undergo activation, clonal expansion, and differentiation into specialized functional subsets of effector T cells. However, to prevent excessive or self-destructive immune responses, regulatory T cells (T(regs)) are instrumental in suppressing the activation and function of effector cells, including effector T cells. The transcription factor Forkhead box P3 (Foxp3) regulates the expression of genes involved in the development and function of T(regs).

Regulatory T cell therapy for the induction of clinical organ transplantation tolerance.

The pursuit of transplantation tolerance is the holygrail in clinical organ transplantation. It has been established that regulatory T cells (Tregs) can confer donor-specific tolerance in mouse models of transplantation. However, this is crucially dependent on the strain combination, the organ transplanted and most importantly, the ratio of Tregs to alloreactive effector T cells.

Regulatory T cells: customizing for the clinic.

Immune-suppressive cellular immunotherapy requires large numbers of antigen-specific regulatory T cells (T(reg) cells), lymphocytes that suppress certain immune responses. Together, three papers in this issue of Science Translational Medicine describe protocols for the ex vivo expansion of human T(reg) cells and assess the immune-suppressive function of ex vivo-manipulated T(reg) cells after transfer into humanized mouse disease models. Along with recent phase I clinical trial results, these new data provide a platform for clinical use of T(reg) cells as personalized therapeutic agents for the treatment of autoimmune diseases, graft-versus-host disease, and transplant rejection.

The yin and yang of signaling in Tregs and TH17 cells.

Substantial advances in our understanding of the developmental and functional relationship between regulatory T cells (T(regs)) and T helper 17 (T(H)17) cells and their potential clinical applications have been made. In response to these breakthroughs, the second international conference entitled "China Tregs/Th17 2010 Shanghai Conference," held in Shanghai, China, was dedicated to this topic. Various types of T(regs) and T(H)17 cells, as well as their relevant cytokines, were discussed.

Th17 and regulatory T cell subsets in diseases and clinical application.

In the past decade it has been established that regulatory T cells (Tregs) control all immune responses. As the induction and effector mechanisms used by Tregs are being unraveled, it is emerging that a reciprocal population of CD4(+) T lymphocytes exists in the immune system that produces inflammatory cytokine IL-17, and coined "Th17 cells". Th17 cells have been implicated in the pathogenesis of many forms of human disease.

Regulatory T cell immunotherapy for transplantation tolerance: step into clinic.

Recent studies in animal models have demonstrated that adoptive transfer of antigen-specific CD4+CD25+ regulatory T cells (Tregs) can prevent or even cure autoimmune diseases, and appear to induce transplantation tolerance. Thus, adoptive cell therapy using ex vivo induced and expanded patient-specific CD4+CD25+Tregs has emerged as a promising individualized medicine for the treatment of inflammatory disease. Here we discuss our current efforts on the pursuit of regulatory T cell therapy for the induction of transplantation tolerance.

Indefinite mouse heart allograft survival in recipient treated with CD4(+)CD25(+) regulatory T cells with indirect allospecificity and short term immunosuppression.

CD4(+)CD25(+) regulatory T cells (Tregs) play a crucial role in controlling immune responses. It is an appealing strategy to harness Tregs for adoptive cell therapy to induce tolerance to allografts. Several approaches have been developed to expand antigen-specific Tregs.

Regulatory T cells: from bench to bedside.

Regulatory T cells (Tregs) are subsets of T cells that are specifically dedicated to controlling immune responses. It has been established that Tregs play a key role in regulating autoimmune disease, allergy, cancer, infectious disease, and in the induction of transplantation tolerance. The latest progress in the development, function, mechanism of action, and homeostasis of regulatory T cells, and their translation to the clinic were presented at the International Conference on Regulatory T Cells and Clinical Application in Human Diseases in Beijing on 25-27 October 2008 (China Tregs 2008).

Regulatory T cells: the cunning fox and its clinical application.

So profound is the potential for regulatory T cells (Tregs) to control unwanted immune responses that in 2008 an entire conference was dedicated to them. The underlying concept of this conference, "China Tregs 2008," was that unraveling the cellular biology of Tregs will lead to important advances for therapies in virtually all human disease processes and in transplantation. The master-switch of immune regulation is the forkhead transcription factor Foxp3; in mice, Foxp3 is a sine qua non for regulatory activity.

Conferring indirect allospecificity on CD4+CD25+ Tregs by TCR gene transfer favors transplantation tolerance in mice.

T cell responses to MHC-mismatched transplants can be mediated via direct recognition of allogeneic MHC molecules on the cells of the transplant or via recognition of allogeneic peptides presented on the surface of recipient APCs in recipient MHC molecules - a process known as indirect recognition. As CD4(+)CD25(+) Tregs play an important role in regulating alloresponses, we investigated whether mouse Tregs specific for allogeneic MHC molecules could be generated in vitro and could promote transplantation tolerance in immunocompetent recipient mice. Tregs able to directly recognize allogeneic MHC class II molecules (dTregs) were obtained by stimulating CD4(+)CD25(+) cells from C57BL/6 mice (H-2(b)) with allogeneic DCs from BALB/c mice (H-2(d)).

Adoptive cell therapy using regulatory T cells as individualized medicine to promote clinical transplantation tolerance.

Despite the success of organ transplantation, most transplant patients are susceptible to variety of infections and cancer due to the use of potent immunosuppressive drugs for life to prevent transplant rejection. Regulatory T cells are capable of preventing transplant rejection while leaving the immune system's function against infection intact. Thus, adoptive cell therapy using patient-specific regulatory T cells as individualized medicine could promote clinical transplantation tolerance without the use of nonspecific immunosuppressive agents.

Generation and expansion of human CD4+ CD25+ regulatory T cells with indirect allospecificity: Potential reagents to promote donor-specific transplantation tolerance.

Background: Harnessing naturally arising CD4+ CD25+ regulatory T cells (Tregs) for potential adoptive cell therapy is hampered by their innate autoreactivity and their limited number.

Methods: CD4+ CD25+ Tregs were purified from peripheral blood of human leukocyte antigen (HLA) DR1*0101+ A2- individuals, and stimulated with autologous monocyte-derived dendritic cells (DCs).

Results: Here we show that CD4+ CD25+ Tregs specific for an HLA A2 (103-120) peptide can be selected from the peripheral blood CD4+ CD25+ T cell population of a healthy individual and detected using a tetramer comprised of HLA DRB1*0101 and the A2 peptide.

CD4+CD25+ regulatory T-cell therapy for allergy, autoimmune disease and transplant rejection.

Naturally occurring CD4+CD25+ regulatory T cells (Tregs) play a critical role in the control of periphery tolerance to self-antigens. Interestingly, they also control immune responses to allergens and transplant antigens. Recent studies in animal models have shown that adoptive transfer of CD4+CD25+ Tregs can prevent or even cure allergic and autoimmune diseases, and appear to induce transplantation tolerance.

In-vitro generation and characterisation of murine CD4+CD25+ regulatory T cells with indirect allospecificity.

Naturally arising CD4(+)CD25(+) regulatory T cells play a pivotal role in the prevention of autoimmunity and in the induction of donor-specific transplantation tolerance. Harnessing regulatory cells for potential adoptive cell therapy is hampered by their lack of antigen-specificity and their limited numbers. Here we describe the generation and expansion of murine CD4(+)CD25(+) T cells with antigen-specificity for an K(d) peptide as potential reagents for adoptive cell therapy in promoting donor-specific transplantation tolerance.

In vitro expanded alloantigen-specific CD4+CD25+ regulatory T cell treatment for the induction of donor-specific transplantation tolerance.

The key goal in clinical transplantation is the induction of donor-specific transplantation tolerance to minimise the morbidity and mortality associated with long-term immunosuppression. Naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) expressing forkhead transcript factor FoxP3 play a crucial role in the prevention of autoimmunity, and appear to mediate transplantation tolerance, and these cells can have indirect allospecificity for donor antigens. Here we show that self-reactive human CD4(+)CD25(+) Tregs can be subverted into allopeptide-specific cells in vitro and be expanded to large cell numbers, and that similar in vitro expanded murine CD4(+)CD25(+) Tregs with indirect allospecificity were capable of inducing donor-specific experimental transplantation tolerance.

New trends in immunosuppression and immunotherapy.

In the past years, research on immune regulation has exploded thanks to the re-emergence of T suppressor cells (Ts), now coined as regulatory T cells (Tregs). It has been established that different populations of Tregs exist in the immune system, and the generation, mechanism of suppression and the cellular and molecular targets of Tregs are being unraveled. This will lead to new opportunities for immune intervention to treat autoimmune disease and to achieve clinical transplantation tolerance.

Regulatory T cells and transplantation tolerance.

In the past decade, several types of regulatory T cells (Tregs) have been identified to play a pivotal role in the control of autoimmunity and transplantation tolerance in rodents and in human beings, including innate regulatory NKT cells and gammadelta T cells, naturally occurring FoxP3 expressing CD4(+)CD25(+) T cells, and in-vitro induced Tregs including interleuking-10 (IL-10)-secreting Tr1 CD4(+) T cells, TGF-beta-producing Th3 CD4(+) T cells, anergic CD4(+) T cells, CD8(+)CD28(-) and CD3(+)CD4(-)CD8(-) T cells. Recent studies have shown that innate and adaptive Tregs may be linked and act in concert to mediate immunosuppression. As our understanding of regulatory T cell populations has substantially advanced, compelling evidence support the prospect that in-vitro expanded, patient-tailored Tregs with indirect anti-donor allospecificity could be potential reagents as adoptive cell therapy for individualized medicine to promote clinical transplantation tolerance.

In vitro-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance.

CD4+CD25+ regulatory T (Treg) cells play a critical role in the induction and maintenance of peripheral immune tolerance. In experimental transplantation models in which tolerance was induced, donor-specific Treg cells could be identified that were capable of transferring the tolerant state to naive animals. Furthermore, these cells appeared to have indirect allospecificity for donor antigens.

CD4+CD25+ regulatory T cell therapy for the induction of donor-specific clinical transplantation tolerance.

Naturally occurring CD4+CD25+ regulatory T cells (Tregs) have been shown to play a key role in the control of autoimmunity. Interestingly, they are also capable of mediating transplantation tolerance and they can have indirect allospecificity for donor antigens. An increasing body of evidence in experimental studies has indicated that adoptive transfer of in vitro expanded CD4+CD25+ Tregs with indirect antidonor allospecificity can induce long-term donor-specific transplantation tolerance.