Judith Alferink
German Cancer Research Center
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Judith Alferink.
Science | 1995
Anna Tafuri; Judith Alferink; Peter Möller; Günter J. Hämmerling; Bernd Arnold
During pregnancy a semiallogeneic fetus survives despite the presence of maternal T cells specific for paternally inherited histocompatibility antigens. A mouse transgenic for a T cell receptor recognizing the major histocompatibility (MHC) antigen H-2Kb was used to follow the fate of T cells reactive to paternal alloantigens. In contrast to syngeneic and third-party allogeneic pregnancies, mice bearing a Kb-positive conceptus had reduced numbers of Kb-reactive T cells and accepted Kb-positive tumor grafts. T cell phenotype and responsiveness were restored after delivery. Thus, during pregnancy maternal T cells acquire a transient state of tolerance specific for paternal alloantigens.
European Journal of Immunology | 1998
Andreas Limmer; Torsten Sacher; Judith Alferink; Marianne Kretschmar; Günter Schönrich; Thomas Nichterlein; Bernd Arnold; Günter J. Hämmerling
Peripheral tolerance is considered to be a safeguard against autoimmunity. Using a TCR‐transgenic mouse system displaying peripheral tolerance against a liver‐specific MHC class I Kb antigen, we investigated whether the breaking of tolerance would result in autoimmunity. Reversal of tolerance was achieved by simultaneous challenge with cells expressing the Kb autoantigen and IL‐2. Tolerance could not be broken with IL‐2 alone or when Kb‐ and IL‐2‐expressing cells were applied to different sites of the mice. However, despite the presence of activated autoreactive T cells that were able to reject Kb‐positive grafts no autoaggression against the Kb‐positive liver was observed. These results indicate that breaking of tolerance per se is not sufficient to cause liver‐specific autoimmunity. However, when in addition to breaking tolerance the mice were infected with a liver‐specific pathogen, autoaggression occurred. Thus, in this system at least two independent steps seem to be required for organ‐specific autoimmunity: reversal of peripheral tolerance resulting in functional activation of autoreactive T cells and conditioning of the liver microenvironment which enables the activated T cells to cause tissue damage.
Proceedings of the National Academy of Sciences of the United States of America | 2012
Karola Poppensieker; David-Marian Otte; Britta Schürmann; Andreas Limmer; Philipp Dresing; Eva Drews; Beatrix Schumak; Luisa Klotz; Jennifer Raasch; Alexander Mildner; Ari Waisman; Stefanie Scheu; Percy A. Knolle; Irmgard Förster; Marco Prinz; Wolfgang Maier; Andreas Zimmer; Judith Alferink
Dendritic cells (DCs) are pivotal for the development of experimental autoimmune encephalomyelitis (EAE). However, the mechanisms by which they control disease remain to be determined. This study demonstrates that expression of CC chemokine receptor 4 (CCR4) by DCs is required for EAE induction. CCR4−/− mice presented enhanced resistance to EAE associated with a reduction in IL-23 and GM-CSF expression in the CNS. Restoring CCR4 on myeloid cells in bone marrow chimeras or intracerebral microinjection of CCR4-competent DCs, but not macrophages, restored EAE in CCR4−/− mice, indicating that CCR4+ DCs are cellular mediators of EAE development. Mechanistically, CCR4−/− DCs were less efficient in GM-CSF and IL-23 production and also TH-17 maintenance. Intraspinal IL-23 reconstitution restored EAE in CCR4−/− mice, whereas intracerebral inoculation using IL-23−/− DCs or GM-CSF−/− DCs failed to induce disease. Thus, CCR4-dependent GM-CSF production in DCs required for IL-23 release in these cells is a major component in the development of EAE. Our study identified a unique role for CCR4 in regulating DC function in EAE, harboring therapeutic potential for the treatment of CNS autoimmunity by targeting CCR4 on this specific cell type.
The International Journal of Neuropsychopharmacology | 2016
Oliver Ambrée; Veerle Bergink; Laura Grosse; Judith Alferink; Hemmo A. Drexhage; Matthias Rothermundt; Volker Arolt; Tom K. Birkenhäger
Background: There is an ongoing search for biomarkers in psychiatry, for example, as diagnostic tools or predictors of treatment response. The neurotrophic factor S100 calcium binding protein B (S100B) has been discussed as a possible predictor of antidepressant response in patients with major depression, but also as a possible biomarker of an acute depressive state. The aim of the present study was to study the association of serum S100B levels with antidepressant treatment response and depression severity in melancholically depressed inpatients. Methods: After a wash-out period of 1 week, 40 inpatients with melancholic depression were treated with either venlafaxine or imipramine. S100B levels and Hamilton Depression Rating Scale (HAM-D) scores were assessed at baseline, after 7 weeks of treatment, and after 6 months. Results: Patients with high S100B levels at baseline showed a markedly better treatment response defined as relative reduction in HAM-D scores than those with low baseline S100B levels after 7 weeks (P=.002) and 6 months (P=.003). In linear regression models, S100B was a significant predictor for treatment response at both time points. It is of interest to note that nonresponders were detected with a predictive value of 85% and a false negative rate of 7.5%. S100B levels were not associated with depression severity and did not change with clinical improvement. Conclusions: Low S100B levels predict nonresponse to venlafaxine and imipramine with high precision. Future studies have to show which treatments are effective in patients with low levels of S100B so that this biomarker will help to reduce patients’ burden of nonresponding to frequently used antidepressants.
Neuroimmunology and Neuroinflammation | 2016
Catharina C. Gross; Diana Ahmetspahic; Tobias Ruck; Andreas Schulte-Mecklenbeck; Kathrin Schwarte; Silke Jörgens; Stefanie Scheu; Susanne Windhagen; Bettina Graefe; Nico Melzer; Luisa Klotz; Volker Arolt; Heinz Wiendl; Sven G. Meuth; Judith Alferink
Objective: To characterize changes in myeloid and lymphoid innate immune cells in patients with relapsing-remitting multiple sclerosis (MS) during a 6-month follow-up after alemtuzumab treatment. Methods: Circulating innate immune cells including myeloid cells and innate lymphoid cells (ILCs) were analyzed before and 6 and 12 months after onset of alemtuzumab treatment. Furthermore, a potential effect on granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)–23 production by myeloid cells and natural killer (NK) cell cytolytic activity was determined. Results: In comparison to CD4+ T lymphocytes, myeloid and lymphoid innate cell subsets of patients with MS expressed significantly lower amounts of CD52 on their cell surface. Six months after CD52 depletion, numbers of circulating plasmacytoid dendritic cells (DCs) and conventional DCs were reduced compared to baseline. GM-CSF and IL-23 production in DCs remained unchanged. Within the ILC compartment, the subset of CD56bright NK cells specifically expanded under alemtuzumab treatment, but their cytolytic activity did not change. Conclusions: Our findings demonstrate that 6 months after alemtuzumab treatment, specific DC subsets are reduced, while CD56bright NK cells expanded in patients with MS. Thus, alemtuzumab specifically restricts the DC compartment and expands the CD56bright NK cell subset with potential immunoregulatory properties in MS. We suggest that remodeling of the innate immune compartment may promote long-term efficacy of alemtuzumab and preserve immunocompetence in patients with MS.
International Journal of Molecular Sciences | 2017
Stefanie Scheu; Shafaqat Ali; Christina Ruland; Volker Arolt; Judith Alferink
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). It affects more than two million people worldwide, mainly young adults, and may lead to progressive neurological disability. Chemokines and their receptors have been shown to play critical roles in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine disease model induced by active immunization with myelin proteins or transfer of encephalitogenic CD4+ T cells that recapitulates clinical and neuropathological features of MS. Chemokine ligand-receptor interactions orchestrate leukocyte trafficking and influence multiple pathophysiological cellular processes, including antigen presentation and cytokine production by dendritic cells (DCs). The C-C class chemokines 17 (CCL17) and 22 (CCL22) and their C-C chemokine receptor 4 (CCR4) have been shown to play an important role in homeostasis and inflammatory responses. Here, we provide an overview of the involvement of CCR4 and its ligands in CNS autoimmunity. We review key clinical studies of MS together with experimental studies in animals that have demonstrated functional roles of CCR4, CCL17, and CCL22 in EAE pathogenesis. Finally, we discuss the therapeutic potential of newly developed CCR4 antagonists and a humanized anti-CCR4 antibody for treatment of MS.
Transgenesis and Targeted Mutagenesis in Immunology | 1994
Bernd Arnold; Günther Schönrich; Iris Ferber; Judith Alferink; Günter J. Hämmerling
Publisher Summary Mature T lymphocytes can be rendered tolerant of antigens expressed outside the thymus. Depending on the tolerogenic signals, T cells reach various levels of tolerance that are distinct because of their capacity for reactivation. Tolerance induction can occur in one step or in several consecutive steps. Distinct mechanisms of extrathymic tolerance differ in their efficiency in protecting against the breakdown of self-tolerance and against autoimmunity. The finding that different tissues can induce different levels of tolerance could explain why some organs are more susceptible to autoimmune diseases than others. Strategies to improve immunosuppression in allograft transplantation and autoimmune diseases should concentrate on suitable methods for eliminating the circulating T cell pool that is responsible for graft rejection or the onset of an autoimmune disease. Because allograft-specific or autoreactive T cells newly exported from the thymus would undergo peripheral tolerance induction, specific immunosuppression could be achieved this way.
Journal of Psychiatry & Neuroscience | 2017
Nils Opel; Ronny Redlich; Dominik Grotegerd; Katharina Dohm; Dario Zaremba; Susanne Meinert; Christian Bürger; Leonie Plümpe; Judith Alferink; Walter Heindel; Harald Kugel; Peter Zwanzger; Volker Arolt; Udo Dannlowski
Background Identifying reliable trait markers of familial risk for major depressive disorder (MDD) is a challenge in translational psychiatric research. In individuals with acute MDD, dysfunctional connectivity patterns of prefrontal areas have been shown repeatedly. However, it has been unclear in which neuronal networks functional alterations in individuals at familial risk for MDD might be present and to what extent they resemble findings previously reported in those with acute MDD. Methods We investigated differences in blood oxygen level–dependent (BOLD) response of the medial orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) to aversive stimuli between acute MDD and familial risk for the disorder in healthy first-degree relatives of acutely depressed patients with MDD (HC-FH+), healthy age- and sex-matched controls without any family history of depression (HC-FH−), and acutely depressed patients with MDD with (MDD-FH+) and without a family history of depression (MDD-FH−) during a frequently used emotional face-matching paradigm. Analyses of task-specific network connectivity were conducted in terms of psychophysiological interactions (PPI). Results The present analysis included a total of 100 participants: 25 HC-FH+, 25 HC-FH−, 25 MDD-FH+ and 25 MDD-FH−. Patients with MDD exhibited significantly increased activation in the medial OFC to negative stimuli irrespective of familial risk status, whereas healthy participants at familial risk and patients with MDD alike showed significant hypoactivation in the DLPFC compared with healthy participants without familial risk. The PPI analyses revealed significantly enhanced task-specific coupling between the medial OFC and differing cortical areas in individuals with acute MDD and those with familial risk for the disorder. Limitations The main limitation of our study is its cross-sectional design. Conclusion Whereas hypoactivation during negative emotion processing in the DLPFC appears as a common feature in both healthy high-risk individuals and acutely depressed patients, activation patterns of the medial OFC and its underlying connectivity seem to distinguish familial risk from acute disorder.
PLOS ONE | 2018
Kim E. Schmidt; Janina M. Kuepper; Beatrix Schumak; Judith Alferink; Andrea Hofmann; Shanshan W. Howland; Laurent Rénia; Andreas Limmer; Sabine Specht; Achim Hoerauf
Malaria ranks among the most important infectious diseases worldwide and affects mostly people living in tropical countries. Mechanisms involved in disease progression are still not fully understood and specific treatments that might interfere with cerebral malaria (CM) are limited. Here we show that administration of doxycycline (DOX) prevented experimental CM (ECM) in Plasmodium berghei ANKA (PbA)-infected C57BL/6 wildtype (WT) mice in an IL-10-independent manner. DOX-treated mice showed an intact blood-brain barrier (BBB) and attenuated brain inflammation. Importantly, if WT mice were infected with a 20-fold increased parasite load, they could be still protected from ECM if they received DOX from day 4–6 post infection, despite similar parasitemia compared to control-infected mice that did not receive DOX and developed ECM. Infiltration of T cells and cytotoxic responses were reduced in brains of DOX-treated mice. Analysis of brain tissue by RNA-array revealed reduced expression of chemokines and tumour necrosis factor (TNF) in brains of DOX-treated mice. Furthermore, DOX-administration resulted in brains of the mice in reduced expression of matrix metalloproteinase 2 (MMP2) and granzyme B, which are both factors associated with ECM pathology. Systemic interferon gamma production was reduced and activated peripheral T cells accumulated in the spleen in DOX-treated mice. Our results suggest that DOX targeted inflammatory processes in the central nervous system (CNS) and prevented ECM by impaired brain access of effector T cells in addition to its anti-parasitic effect, thereby expanding the understanding of molecular events that underlie DOX-mediated therapeutic interventions.
Archive | 2018
Janina M. Kuepper; Kim E. Schmidt; Beatrix Schumak; Judith Alferink; Sabine Specht; Achim Hoerauf
Malaria is still one of most important infectious diseases despite intensive research and decreasing numbers of fatalities. Among the various outcomes caused by different Plasmodium strains, cerebral malaria (CM) caused by Plasmodium falciparum is the most severe and accounts for almost all malaria [for full text, please go to the a.m. URL]