scispace - formally typeset
Search or ask a question
Author

Anna Maria Wolf

Bio: Anna Maria Wolf is an academic researcher from Innsbruck Medical University. The author has contributed to research in topics: Cytokine & Immune system. The author has an hindex of 31, co-authored 51 publications receiving 5402 citations. Previous affiliations of Anna Maria Wolf include University Hospital Bonn & Austrian Academy of Sciences.


Papers
More filters
01 Jan 2003
TL;DR: Evidence is provided of an increased pool of CD4(+)CD25(+) regulatory T cells in the peripheral blood of cancer patients with potent immunosuppressive features, which should be considered for the design of immunomodulatory therapies such as dendritic cell vaccination.
Abstract: Purpose: T cells constitutively expressing both CD4 and CD25 are essential for maintenance of self-tolerance and therefore have been referred to as regulatory T cells (Treg). Experimental tumor models in mice revealed that Tregs are potent inhibitors of an antitumor immune response. The current study was designed to determine whether cancer patients exhibit an expanded Treg pool. Experimental Design: The frequency of Tregs in the peripheral blood of 42 patients suffering from epithelial malignancies and from 34 healthy controls was determined by flow cytometry. The immunoregulatory properties of CD4CD25 and CD4CD25 T cells were characterized by proliferation and suppression assays. Cocultures with natural killer (NK) cells were performed to determine the impact of Tregs on NK-mediated cytotoxicity. Results: Patients with epithelial malignancies show an increase of CD4CD25 T cells in the peripheral blood with characteristics of Tregs, i.e., they are CD45RA, CTLA-4, and transforming growth factor . Notably, CD4 T cells from cancer patients are characterized by an impaired proliferative capacity, which is restored to the extend of CD25depleted CD4 T cells from control persons by prior removal of CD25 T cells. In contrast to CD4CD25 T cells, isolated CD4CD25 T cells from cancer patients were anergic towards T cell receptor stimulation. In addition, CD4CD25 T cells suppressed the proliferation of CD4CD25 T cells. When cultured together with CD56 NK-cells, CD4CD25 T cells from cancer patients effectively inhibited NK-cell-mediated cytotoxicity. Conclusions: Thus, we provide evidence of an increased pool of CD4CD25 regulatory T cells in the peripheral blood of cancer patients with potent immunosuppressive features. These findings should be considered for the design of immunomodulatory therapies such as dendritic cell vaccination.

779 citations

Journal ArticleDOI
TL;DR: The presented data support the idea that adiponectin might be of critical relevance for cytokine regulation in obesity and fatty liver diseases affecting primarily macrophage functions and could represent a fundamental link between over-nutrition and an impaired inflammatory immune response.

768 citations

Journal Article
TL;DR: In this article, the frequency of Tregs in the peripheral blood of 42 patients suffering from epithelial malignancies and from 34 healthy controls was determined by flow cytometry.
Abstract: Purpose: T cells constitutively expressing both CD4 and CD25are essential for maintenance of self-tolerance and therefore have been referred to as regulatory T cells (Treg). Experimental tumor models in mice revealed that Tregs are potent inhibitors of an antitumor immune response. The current study was designed to determine whether cancer patients exhibit an expanded Treg pool. Experimental Design: The frequency of Tregs in the peripheral blood of 42 patients suffering from epithelial malignancies and from 34 healthy controls was determined by flow cytometry. The immunoregulatory properties of CD4 + CD25 + and CD4 + CD25 − T cells were characterized by proliferation and suppression assays. Cocultures with natural killer (NK) cells were performed to determine the impact of Tregs on NK-mediated cytotoxicity. Results: Patients with epithelial malignancies show an increase of CD4 + CD25 + T cells in the peripheral blood with characteristics of Tregs, i.e. , they are CD45RA − , CTLA-4 + , and transforming growth factor β + . Notably, CD4 + T cells from cancer patients are characterized by an impaired proliferative capacity, which is restored to the extend of CD25-depleted CD4 + T cells from control persons by prior removal of CD25 + T cells. In contrast to CD4 + CD25 − T cells, isolated CD4 + CD25 + T cells from cancer patients were anergic towards T cell receptor stimulation. In addition, CD4 + CD25 + T cells suppressed the proliferation of CD4 + CD25 − T cells. When cultured together with CD56 + NK-cells, CD4 + CD25 + T cells from cancer patients effectively inhibited NK-cell-mediated cytotoxicity. Conclusions: Thus, we provide evidence of an increased pool of CD4 + CD25 + regulatory T cells in the peripheral blood of cancer patients with potent immunosuppressive features. These findings should be considered for the design of immunomodulatory therapies such as dendritic cell vaccination.

762 citations

Journal ArticleDOI
TL;DR: High expression levels of FoxP3 might represent a surrogate marker for an immunosuppressive milieu contributing to tumor immune escape and strategies selectively depleting Treg might improve the antitumor activity of endogenously arising tumor-reactive T cells and immunotherapies using vaccines or antibodies.
Abstract: Purpose: The forkhead box transcription factor FoxP3 is specifically expressed in T cells with regulatory properties (Treg). Recently, high numbers of Treg were described to be associated with poor survival in different malignancies. The aim of the presented study was determine the prognostic effect of FoxP3 mRNA expression (reflecting the tissue content of Treg) in ovarian carcinoma and its relation with cytokines, such as IFN-γ. Experimental Design: Total RNA was isolated from 99 ovarian carcinoma and from 14 healthy ovarian biopsies. Real-time PCR for FoxP3 was done and correlated with IFN-γ-, CD3-, IRF-1-, SOCS-1-, HER-2-, and iNOS expression as well as patients9 outcome. The mRNA data was corroborated by FoxP3 immunohistochemistry. Results: Quantitation of FoxP3 expression identified a patient subgroup (>81th percentile), which is characterized by a significantly worse prognosis in terms of overall survival (27.8 versus 77.3 months, P = 0.0034) and progression-free survival (18 versus 57.5 months; P = 0.0041). FoxP3 expression correlated with IFN-γ, IRF-1, and CD3 expression. High FoxP3 expression represents an independent prognostic factor for overall survival ( P = 0.004) and progression-free survival ( P = 0.004). Conclusions: High expression levels of FoxP3 might represent a surrogate marker for an immunosuppressive milieu contributing to tumor immune escape. Strategies selectively depleting Treg might improve the antitumor activity of endogenously arising tumor-reactive T cells and immunotherapies using vaccines or antibodies.

510 citations

Journal ArticleDOI
01 Nov 2011-Diabetes
TL;DR: Data suggest a potential therapeutic value of Tregs to improve insulin resistance and end organ damage in type 2 diabetes by limiting the proinflammatory milieu.
Abstract: OBJECTIVE To assess the potential role of FoxP3-expressing regulatory T cells (Tregs) in reversing obesity-linked insulin resistance and diabetic nephropathy in rodent models and humans. RESEARCH DESIGN AND METHODS To characterize the role of Tregs in insulin resistance, human visceral adipose tissue was first evaluated for Treg infiltration and second, the db/db mouse model was evaluated. RESULTS Obese patients with insulin resistance displayed significantly decreased natural Tregs but an increase in adaptive Tregs in their visceral adipose tissue as compared with lean control subjects. To further evaluate the pathogenic role of Tregs in insulin resistance, the db/db mouse model was used. Treg depletion using an anti-CD25 monoclonal antibody enhanced insulin resistance as shown by increased fasting blood glucose levels as well as an impaired insulin sensitivity. Moreover, Treg-depleted db/db mice developed increased signs of diabetic nephropathy, such as albuminuria and glomerular hyperfiltration. This was paralleled by a proinflammatory milieu in both murine visceral adipose tissue and the kidney. Conversely, adoptive transfer of CD4+FoxP3+ Tregs significantly improved insulin sensitivity and diabetic nephropathy. Accordingly, there was increased mRNA expression of FoxP3 as well as less abundant proinflammatory CD8+CD69+ T cells in visceral adipose tissue and kidneys of Treg-treated animals. CONCLUSIONS Data suggest a potential therapeutic value of Tregs to improve insulin resistance and end organ damage in type 2 diabetes by limiting the proinflammatory milieu.

254 citations


Cited by
More filters
Journal ArticleDOI
TL;DR: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors.
Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

6,968 citations

Journal ArticleDOI
TL;DR: The number of circulating tumor cells before treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer.
Abstract: Metastatic breast cancer (MBC) is considered incurable; therefore, palliative treatment is the only option. The biologic heterogeneity of the disease is reflected in its somewhat unpredictable clinical behavior. The presence of circulating tumor cells (CTCs) in patients with MBC about to start a new line of treatment has been shown to predict progression-free and overall survival. This prognostic value is independent of the line of therapy (eg, first or second line). Moreover, a multivariate analysis has shown the prognostic value of CTCs to be superior to that of site of metastasis, type of therapy, and length of time to recurrence after definitive primary surgery. These data suggest that the presence of CTCs may be used to modify the staging system for advanced disease. Larger studies are needed to confirm these data and evaluate the use of CTC detection in monitoring treatment and furthering our understanding of breast cancer biology when combined with other diagnostic technologies.

4,244 citations

Journal ArticleDOI
TL;DR: Diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.
Abstract: Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or "alternatively activated" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or "classically activated" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.

4,046 citations

Journal ArticleDOI
TL;DR: The discovery that obesity itself results in an inflammatory state in metabolic tissues ushered in a research field that examines the inflammatory mechanisms in obesity, and metaflammation is summarized, defined as low-grade, chronic inflammation orchestrated by metabolic cells in response to excess nutrients and energy.
Abstract: The modern rise in obesity and its strong association with insulin resistance and type 2 diabetes have elicited interest in the underlying mechanisms of these pathologies. The discovery that obesity itself results in an inflammatory state in metabolic tissues ushered in a research field that examines the inflammatory mechanisms in obesity. Here, we summarize the unique features of this metabolic inflammatory state, termed metaflammation and defined as low-grade, chronic inflammation orchestrated by metabolic cells in response to excess nutrients and energy. We explore the effects of such inflammation in metabolic tissues including adipose, liver, muscle, pancreas, and brain and its contribution to insulin resistance and metabolic dysfunction. Another area in which many unknowns still exist is the origin or mechanism of initiation of inflammatory signaling in obesity. We discuss signals or triggers to the inflammatory response, including the possibility of endoplasmic reticulum stress as an important contributor to metaflammation. Finally, we examine anti-inflammatory therapies for their potential in the treatment of obesity-related insulin resistance and glucose intolerance.

3,045 citations

Journal ArticleDOI
TL;DR: Several adipocytokines have a central role in the regulation of insulin resistance, as well as many aspects of inflammation and immunity, and understanding this rapidly growing family of mainly adipocyte-derived mediators might be of importance in the development of new therapies for obesity-associated diseases.
Abstract: There has been much effort recently to define the role of adipocytokines, which are soluble mediators derived mainly from adipocytes (fat cells), in the interaction between adipose tissue, inflammation and immunity. The adipocytokines adiponectin and leptin have emerged as the most abundant adipocyte products, thereby redefining adipose tissue as a key component not only of the endocrine system, but also of the immune system. Indeed, as we discuss here, several adipocytokines have a central role in the regulation of insulin resistance, as well as many aspects of inflammation and immunity. Other adipocytokines, such as visfatin, have only recently been identified. Understanding this rapidly growing family of mainly adipocyte-derived mediators might be of importance in the development of new therapies for obesity-associated diseases.

2,855 citations