Andreas Thiel

Charité Universitätsmedizin Berlin | Charité · Regenerative Immunology and Aging

SARS-CoV-2 mRNA vaccination of healthy individuals is highly immunogenic and protective against severe COVID-19. However, there are limited data on how disease-modifying therapies (DMTs) alter SARS-CoV-2 mRNA vaccine immunogenicity in patients with autoimmune diseases. Here we investigated the induction and stability of vaccine-specific antibodies,...

Advanced age is a main risk factor for severe COVID-19. However, low vaccination efficacy and accelerated waning immunity have been reported in this age group. To elucidate age-related differences in immunogenicity, we analyzed human cellular, serological, and salivary SARS-CoV-2 spike glycoprotein-specific immune responses to the BNT162b2 COVID-19...

The development of atopic dermatitis (AD) in infancy, and subsequent allergic rhinitis, food allergies, and asthma in later childhood, is known as the atopic march. The mechanism is largely unknown, yet the course of disease indicates the contribution of inter-epithelial crosstalk, through to the onset of inflammation in the skin and progression to...

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, and it remains unclear whether T cells contribute to disease pathology. Here, we combined single-cell transcriptomics and single-cell proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly a...

Advanced age is a main risk factor for severe COVID-19 and thus elderly were often prioritized for vaccination. However, low vaccination efficacy and accelerated waning immunity have been reported in this age group. To elucidate age-related differences in immunogenicity, we analysed cellular, serological and salivary SARS-CoV-2 spike glycoprotein-s...

Cross-reactive T cells aid in the fight There is mounting evidence that immunological memory after infection with seasonal human coronaviruses (hCoVs) contributes to cross-protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Loyal et al . identified a universal immunodominant coronavirus peptide found within the fusion p...

Purpose The study ‘Sex- and gender-sensitive prevention of cardiovascular and metabolic disease in older adults in Germany’, the GendAge study, focuses on major risk factors for cardiovascular and metabolic diseases and on the development of major outcomes from intermediate phenotypes in the context of sex and gender differences. It is based on a f...

An amendment to this paper has been published and can be accessed via the original article.

Birdshot Retinochoroiditis (BSRC) is a progressive non-infectious intraocular inflammation that affects choroid and retina. Inflammatory processes have adverse effects on vision by affecting photoreceptor-bearing cells that do not regenerate. This study aimed at characterizing inflammatory CD4+ and CD8+ T cell subsets in the peripheral blood of act...

Background Immune ageing is a result of repetitive microbial challenges along with cell intrinsic or systemic changes occurring during ageing. Mice under ‘specific-pathogen-free’ (SPF) conditions are frequently used to assess immune ageing in long-term experiments. However, physiological pathogenic challenges are reduced in SPF mice. The question a...

While evidence for pre-existing SARS-CoV-2-cross-reactive CD4+ T cells in unexposed individuals is increasing, their functional significance remains unclear. Here, we comprehensively determined SARS-CoV-2-cross-reactivity and human coronavirus-reactivity in unexposed individuals. SARS-CoV-2-cross-reactive CD4+ T cells were ubiquitous, but their pre...

Purpose: Birdshot Retinochoroiditis (BSRC) is a progressive non-infectious intraocular inflammation that affects choroid and retina. Inflammatory processes have adverse effects on vision by affecting photoreceptor-bearing cells that do not regenerate. Methods: This study aimed at characterizing inflammatory CD4⁺ and CD8⁺ T cell subsets in the perip...

The prevailing ‘division of labor’ concept in cellular immunity is that CD8⁺ T cells primarily utilize cytotoxic functions to kill target cells, while CD4⁺ T cells exert helper/inducer functions. Multiple subsets of CD4⁺ memory T cells have been characterized by distinct chemokine receptor expression. Here, we demonstrate that analogous CD8⁺ memory...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic1,2. Clinical manifestations of COVID-19 vary, ranging from asymptomatic infection to respiratory failure. The mechanisms determining such variable outcomes remain unresolved. Here, we investigated SARS-CoV-2 spi...

The study Sex- and gender-sensitive prevention of cardiovascular and metabolic disease in older adults in Germany, the GendAge study, focusses on major risk factors for cardiovascular and metabolic diseases and on the development of major outcomes from intermediate phenotypes in the context of biological sex and gender differences. It is based on a...

Pluripotent stem cells (PSCs) are promising candidates for cell-based regenerative therapies. To avoid rejection of transplanted cells, several approaches are being pursued to reduce immunogenicity of the cells or modulate the recipient's immune response. These include gene editing to reduce the antigenicity of cell products, immunosuppression of t...

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a rapidly unfolding pandemic, overwhelming health care systems worldwide1. Clinical manifestations of Corona-virus-disease 2019 (COVID-19) vary broadly, ranging from asymptomatic infection to acute respiratory failure and death2, yet the underlying physiological conditions...

Antibody‐mediated diseases affect more than 10% of the human population. For most, no cure is available, particularly when the pathogenic antibodies are secreted by long‐lived plasma cells resistant to conventional immunosuppressive therapies. Current therapeutic approaches target not only the plasma cells that secrete pathogenic antibodies, but al...

Adeno‐associated virus serotype 8 (AAV8) gene therapy has shown efficacy in several clinical trials and is considered a highly promising technology to treat monogenic diseases such as hemophilia A and B. However, a major drawback of AAV8 gene therapy is that it can be applied only once because anti‐AAV8 immunity develops after the first treatment....

Background: Graft-versus-host disease (GvHD) presents a major cause for morbidity and mortality after allogeneic hematopoietic stem cell transplantation (alloHSCT). Rabbit anti-thymocyte globulin (rATG) treatment reduces the incidence of GvHD after alloHSCT. However, delayed immune reconstitution following rATG treatment, partly due to hampered th...

Influenza vaccination is a common approach to prevent seasonal and pandemic influenza. Pre-existing antibodies against close viral strains might impair antibody formation against previously unseen strains–a process called original antigenic sin. The role of this pre-existing cellular immunity in this process is, despite some hints from animal model...

In Myasthenia Gravis (MG) thymic pathologies are often present and thymectomy is used as treatment. By flow cytometry we elucidated alterations of naïve CD4⁺ T cell homeostasis in MG patients and patients with thymoma. MG patients showed increased absolute numbers of CD31- centralnaïve CD4⁺ T cells. Thymoma patients displayed a significantly higher...

Background Over the past 20 years, hematopoietic stem cell transplantation (HSCT) has been emerging as a promising treatment option for severe cases of autoimmune diseases (ADs). Meanwhile, positive results have been obtained in 3 randomised clinical trials for systemic sclerosis. The goal of this therapy is to induce medication-free remissions by...

There are currently limited insights into the progression of human primary humoral immunity despite numerous studies in experimental models. In this study, we analyzed a primary and related secondary parenteral keyhole limpet hemocyanin (KLH) immunization in five human adults. The primary challenge elicited discordant KLH-specific serum and blood e...

Purpose To investigate the therapeutic relevance of targeting long-lived plasma cells (PC), which contribute to the chronicity of SLE through continuous secretion of pathogenic antibodies, using immunoablation with antithymocyte-globulin (ATG) in the context of haematopoietic stem cell transplantation (HSCT) or proteasome inhibition with Bortezomib...

Immunosenescence is a hallmark of the aging immune system and is considered the main cause of a reduced vaccine efficacy in the elderly. Although γδ T cells can become activated by recombinant influenza hemagglutinin, their age-related immunocompetence during a virus-induced immune response has so far not been investigated. In this study we evaluat...

Kinetics of absolute counts and frequencies. Vaccination-dependent kinetics of absolute counts and frequencies of the γδ T cell subsets in Figs 2 and 3A) Absolute counts of γδTCR+Ki67+. B) Absolute counts of γδTCR+CD38+Ki67+. C) Frequency of total CD38+ among γδTCR+ T cells. D) Frequency of CD38+Ki67– among γδTCR+ T cells. The box represents the 25...

Association of frequencies to day 21 HAI titers of B/Brisbane/60/2008. Association of day 21 HAI titers of B/Brisbane/60/2008-like virus to A) the frequency of total Ki67+ among γδTCR+ and B) the frequency of CD38+Ki67+ among γδTCR+ at day 3 and 7 for the young and the elderly. Correlation by the Spearman rank method. Each point indicates a donor....

Association of proportionality constant and day 21 HAI titers. Association of day 0–3 proportionality constant of the frequency of total Ki67+ among γδTCR+ T cells and frequency of CD38+Ki67+ among γδTCR+ T cells for young and elderly (Fig 2B and 2E) to the day 21 HAI titers of the A) and D) A/California/7/2009 (H1N1), B) and E) A/Perth/16/2009 (H3...

Characterization of activation of γδ T cells. A) The gating strategy applied to identify activated γδTCR+ T cells. Shown is a representative donor. B and C) Activation status of γδTCR+ T cells at baseline in the young donors in Fig 1B separated into low (< 10%) and high (> = 10%) baseline frequency of γδTCR+ T cells. D) Representative Ki67 stain at...

CMV status and kinetics of absolute counts and frequencies. Vaccination-dependent kinetics of absolute counts and frequencies of the γδ T cell subsets in Figs 2 and 3, with age groups subdivided into CMV negative and CMV positive. A) Frequency of total Ki67+ among γδTCR+ T cells. B) Frequency of CD38+Ki67+ among γδTCR+ T cells. C) Absolute counts o...

A great part of our knowledge on mammalian immunology has been established in laboratory settings. The use of inbred mouse strains enabled controlled studies of immune cell and molecule functions in defined settings. These studies were usually performed in specific-pathogen free (SPF) environments providing standardized conditions. In contrast, mam...

Understanding the immune response after vaccination against new influenza strains is highly important in case of an imminent influenza pandemic and for optimization of seasonal vaccination strategies in high risk population groups, especially the elderly. Models predicting the best sero-conversion response among the three strains in the seasonal va...

Logistic regression models with monocytes (CD14+), natural killer (CD56+ NK) cells, dendritic cells (pDCs), plasmablasts and influenza specific activated (CD4+CD40L+) cells in the pilot study. Plasmablasts counts are significantly (p = 0.03) different between H1N1 protected and non-protected vaccinees, while the other sub-populations in this figure...

Prediction of non-protection to A(H1N1)pdm09 strain as function of the combination of age, NSSN, CD4+ T cells and B cells in the pilot study. Using multi-variate logistic regression shows that the combination of age, number of sero-negative strains (NSSN), CD4+ T-cell counts and B-cell counts at baseline give a predictive model with high significan...

Gating strategy for identification of B-cell subsets. The figure is showing the gating strategy for the identification of CD19+ B-cells and its subsets. M = Memory, N = Naive. (TIF)

Gating strategy for identification of regulatory T-cell populations. The figure is showing the gating strategy for the identification of regulatory T-cell populations. nTreg = natural regulatory T-cells, N = Naïve, M = Memory. (TIF)

Gating strategy for identification of Plasmablasts. The figure is showing the gating strategy for the identification of Plasmablasts. (TIF)

Hierarchical network representation of immune cell-subset counts at baseline with respect to the Perth strain protection in the pilot study. Overall, 36 immune cell subsets at baseline were analyzed and compared in Perth sero-negative donors with or without sero-protection for the Perth strain after vaccination using the Wilcoxon test. P-values bel...

Baseline immune cell counts as a function of age in the pilot study. The counts of CD8+ T cells and Monocytes are significantly different between young and old donors (two-sided Wilcoxon test, p<0.05). (TIF)

Baseline immune cell counts as a function of NSSN in the pilot study. No significant differences related to the number of sero-negative strains were observed in A(H1N1)pdm09 sero-negative donors. (TIF)

Pilot study data. The table includes all data which were used to do the analysis presented in the paper for the pilot study. The first three columns contain the ids, the age (in years) and the gender (F-female, M-male) of the donors. The following six columns show the HAI titer for each virus strain prior to (day0) and after (day21) vaccination. Pl...

Logistic regression models with age only, CD4+ T cells, Lymphocytes and Leukocytes in the pilot study. Age, CD4 T-cell and lymphocyte counts are significantly (p = 0.01, p = 0.04 and p = 0.05, respectively) different between H1N1 protected and non-protected vaccinees, while leukocytes show no significant association with protection on their own. Le...

Gating strategy for identification of Dendritic cells. The figure is showing the gating strategy for the identification of Dendritic cell populations. C = Classical Monocytes, NC—Non-classical Monocytes, T = Transitional Monocytes, pDC = plasmacytoide dendritic cells, mDC = myeloide dendritic cells. (TIF)

Gating strategy for identification of Natural Killer cells (NK). The figure is showing the gating strategy for the identification of Natural Killer cells. (TIF)

Gating strategy for identification of influenza specific CD4+CD40L+ cells. The figure is showing the gating strategy for the identification of influenza specific CD4+CD40L+ cells. (TIF)

Hierarchical network representation of immune cell-subset counts at baseline with respect to the Brisbane strain protection in the pilot study. Overall, 36 immune cell subsets at baseline were analyzed and compared in Brisbane sero-negative donors with or without sero-protection for the Brisbane strain after vaccination using the Wilcoxon test. P-v...

Logistic regression models with CD4+ T cells, naive CD4+ T cells, naive CD4+CD31+ recent thymic emigrants T cells (RTE) and naive CD4+CD31- non-RTE T cells in the pilot study. Counts of CD4 total T-cells, CD4 Naive T-cells, CD4 Naïve RTE T-cells and CD4 Naïve non-RTE T-cells are all significantly (p = 0.02, p = 0.002, p = 0.009 and p = 0.005, respe...

Gating strategy for identification of T-cell subsets. The figure is showing the gating strategy for the identification of CD3+ T-cells and its subsets CD4+ and CD8+ T-cells. EM = Effector Memory, CM = Central Memory, Eff = Effector, N = Naïve, RTE = Recent Thymic Emigrants. (TIF)

Gating strategy for identification of proliferating CD4+ and CD8+ cells. The figure is showing the gating strategy for the identification of CD4+Ki67+ and CD8+Ki67+ cells. (TIF)

Validation study data. The table includes all data which were used to do the analysis presented in the paper for the validation study. The first three columns contain the ids, the age (in years) and the gender (F-female, M-male) of the donors. The following six columns show the HAI titer for each virus strain prior to (day0) and after (day21) vacci...

The term "immunosenescence" defines gradual alterations of human immune functions associated with advancing age. Decreasing immunocompetence results in a higher susceptibility to infections and rising incidences of certain malignant and autoimmune diseases in elderly humans. As a major signature for immunosenescence, decreased vaccination efficienc...

Plasmacytoid dendritic cells (pDCs) play a central role in the pathogenesis of systemic lupus erythematosus (SLE) as IFN-α producers and promoters of T-cell activation or tolerance. Here, we demonstrated by flow-cytometry and confocal microscopy that Siglec-1, a molecule involved in the regulation of adaptive immunoresponses, is expressed in a subs...

Immunological competence declines progressively with age, resulting in increased susceptibility of the elderly to infection and impaired responses to vaccines. Underlying mechanisms remain largely obscure as they have been related to complex, individual systemic immune properties that are challenging to investigate. In this study, we explored age-r...

Immunosenescence results from a continuous deterioration of immune responses resulting in a decreased response to vaccines. A well-described age-related alteration of the immune system is the decrease of de novo generation of T and B cells. In addition, the accumulation of memory cells and loss of diversity in antigen specificities resulting from a...

Immunosenescence is a hallmark of the aging immune system, leading to increased susceptibility to infections in the aged population and decreased ability to eradicate infectious pathogens. These effects, in turn, result in an increased burden on the healthcare system due to elevated frequency and duration of hospital visits. Growing evidence sugges...

Besides growing plants, eating a lot and drinking beer, Tolkien's Hobbits enjoy maintaining a quiet state. Regarding the latter, the name chosen for a recently discovered transcription factor seems to be unintentionally appropriate. The zinc finger protein ZNF683 was originally named “Hobit” for Homolog of Blimp-1 in T cells. In this issue of the E...

The efficacy of immunotherapy in cancer patients is influenced by differences in their immune status. An evaluation of immunocompetence before therapy may help to predict therapeutic success and guide the selection of appropriate regimens. We assessed the preexisting cellular immunity against prostate-specific antigen (PSA) in untreated prostate ca...

Although our knowledge on the immune system and immunological memory has expanded enormously during the last decades, the development of strategies to induce robust protective memory against infections and tumors remains challenging. Intense efforts and immense resources have been put into the development of vaccines. However, effective tools to as...

Oral tolerance is the antigen-specific inhibition of a systemic immune response after oral antigen uptake and well established in animal models. We recently showed that KLH feeding modulates subsequently induced systemic immune responses in humans as well. In the present study, we investigated whether oral KLH can also modulate pre-existing antigen...

Th17-derived Th1 lymphocytes, termed nonclassic, differ from classic Th1 cells because of the presence of retinoic acid orphan receptor (ROR)C2 and the surface expression of CD161 and CCR6. We demonstrate in this article that nonclassic Th1 cells, like Th17 cells, have a marked RORC2 and IL17A demethylation, whereas classic Th1 cells exhibit a comp...

The role of Th17 cells in the pathogenesis of autoantibody-mediated diseases is unclear. Here, we assessed the contribution of Th17 cells to the pathogenesis of experimental autoimmune myasthenia gravis (EAMG), which is induced by repetitive immunizations with Torpedo californica acetylcholine receptor (tAChR). We show that a significant fraction o...

It is believed that memory CD8(+) T cells are maintained in secondary lymphoid tissues, peripheral tissues and bone marrow by homeostatic proliferation. Their survival has been shown to be dependent on interleukin-7 (IL-7), but it is unclear where they acquire it. Here we show that in murine bone marrow, memory CD8(+) T cells individually colocaliz...

Plasma cells (PCs) are antibody-secreting cells (ASCs) that play an important role in immunity and autoimmunity. There is an urgent need to develop efficient and simple methods for analyzing the biology and function of PCs at the single-cell level. Here, we describe a method for the selective labeling of viable cells secreting antibodies of a given...

CD40 is frequently expressed on malignant cells of different origin. Due to the observed antitumorigenic effects induced after CD40 engagement it represents an attractive target for immunotherapies. We demonstrate here that CD40L expressing tumor-specific CD8+ T-cell population can act as potent physiological CD40 agonist against CD40 expressing tu...

Many societies across the world are confronted with demographic changes, usually related to increased life expectancy and, often, relatively low birth rates. Information and communication technologies (ICT) may contribute to adequately support senior citizens in aging societies with respect to quality of life and quality and efficiency of health ca...

The Lower Saxony Research Network “Design of Environments for Ageing” (GAL) studied possible applications of assistive technology for enabling older adults to live longer and independent in their own home. As part of this work, a technical platform was developed as a common technical basis for all assistive systems in the project. This article pres...

This article describes the results of field studies performed over a period between five months and 24 months. The objectives of these studies were to collect long-term real-life data to evaluate how these data can be mapped to items on standardized assessment tests and which presentation method is most suitable to inform caregivers about critical...