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  1. Article ; Online: Donor-derived IL-17A and IL-17F deficiency triggers Th1 allo-responses and increases gut leakage during acute GVHD.

    Ivan Odak / Alina Depkat-Jakob / Maleen Beck / Michael Jarek / Yan Yu / Ursula Seidler / Sascha David / Arnold Ganser / Reinhold Förster / Immo Prinz / Christian Koenecke

    PLoS ONE, Vol 15, Iss 4, p e

    2020  Volume 0231222

    Abstract: IL-17A and IL-17F cytokines are important regulators of acute graft-versus-host-disease (GVHD). However, contrary effects of these cytokines in inflammatory diseases have been reported. To investigate the effects of donor-derived IL-17A and IL-17F on ... ...

    Abstract IL-17A and IL-17F cytokines are important regulators of acute graft-versus-host-disease (GVHD). However, contrary effects of these cytokines in inflammatory diseases have been reported. To investigate the effects of donor-derived IL-17A and IL-17F on GVHD, we made use of single (Il17a-/- or Il17f-/-) and double deficient (Il17af-/-) allogeneic donor CD4+ T cells. We could demonstrate that transplantation of Il17af-/- CD4+ donor T cells led to aggravated GVHD. However, this phenotype was not observed after transplantation of single, Il17a-/- or Il17f-/-, deficient CD4+ T cells, suggesting redundant effects of IL-17A and IL-17F. Moreover, Il17af-/- cell recipients showed an increase of systemic IFNγ, indicating a heightened pro-inflammatory state, as well as infiltration of IFNγ-secreting CD4+ T cells in the recipients' intestinal tract. These recipients exhibited significant gut leakage, and markedly macrophage infiltration in the gastrointestinal epithelial layer. Moreover, we saw evidence of impaired recovery of gut epithelial cells in recipients of Il17af-/- CD4+ T cells. In this study, we show that IL-17A/F double deficiency of donor CD4+ T cells leads to accelerated GVHD and therefore highlight the importance of these cytokines. Together, IL-17 cytokines might serve as a brake to an intensified Th1 response, leading to the exacerbated gut damage in acute GVHD.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610 ; 570
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: VH1 Family Immunoglobulin Repertoire Sequencing after Allogeneic Hematopoietic Stem Cell Transplantation.

    Maya K Sethi / Felicitas Thol / Michael Stadler / Michael Heuser / Arnold Ganser / Christian Koenecke / Oliver Pabst

    PLoS ONE, Vol 12, Iss 1, p e

    2017  Volume 0168096

    Abstract: After allogeneic hematopoietic stem cell transplantation (HSCT), recovery of humoral immunity is essential to protect from life-threatening infections. However, monitoring the humoral immune system after transplantation with standard techniques in the ... ...

    Abstract After allogeneic hematopoietic stem cell transplantation (HSCT), recovery of humoral immunity is essential to protect from life-threatening infections. However, monitoring the humoral immune system after transplantation with standard techniques in the clinical routine is imprecise. Here, we performed sequencing of mononuclear bone marrow cells to characterize the VH1-repertoire of switched B cells of healthy volunteers and patients undergoing HSCT. Analysis of healthy bone marrow donors and patients showed virtually no clonally related sequences between individuals. Interestingly, clonally related sequences were present in pre- and post-transplantation bone marrow of patients undergoing HSCT for acute myeloid leukemia treatment. We consistently observed such related B cell clones, irrespective of conditioning regimen, donor source or time post transplantation. In general, repertoire diversity was lower in post-HSCT as compared to pre-HSCT samples. However, post-HSCT repertoires retained highly mutated sequences, despite immunosuppressive therapy and presence of T cell deficiency after HSCT. These observations identify key properties of the recovering B cell compartment and provide a conceptual framework for the surveillance of humoral immunity after allogeneic transplantation.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Reappearance of effector T cells is associated with recovery from COVID-19

    Ivan Odak / Joana Barros-Martins / Berislav Bošnjak / Klaus Stahl / Sascha David / Olaf Wiesner / Markus Busch / Marius M. Hoeper / Isabell Pink / Tobias Welte / Markus Cornberg / Matthias Stoll / Lilia Goudeva / Rainer Blasczyk / Arnold Ganser / Immo Prinz / Reinhold Förster / Christian Koenecke / Christian R. Schultze-Florey

    EBioMedicine, Vol 57, Iss , Pp 102885- (2020)

    2020  

    Abstract: Background: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. Methods: 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC) participated in ... ...

    Abstract Background: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. Methods: 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC) participated in this study. We used two comprehensive 11-colour flow cytometric panels conforming to Good Laboratory Practice and approved for clinical diagnostics. Findings: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and γδ T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. Interpretation: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Understanding T cell-responses in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control. Funding: Funded by State of Lower Saxony grant 14–76,103–184CORONA-11/20 and German Research Foundation, Excellence Strategy – EXC2155“RESIST”–Project ID39087428, and DFG-SFB900/3–Project ID158989968, grants SFB900-B3, SFB900-B8.
    Keywords SARS-CoV-2 ; COVID-19 ; Severity ; Outcome ; T cells ; T cell memory ; Medicine ; R ; Medicine (General) ; R5-920 ; covid19
    Subject code 610
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Single-Cell Transcriptomics Identifies the Adaptation of Scart1+ Vγ6+ T Cells to Skin Residency as Activated Effector Cells

    Likai Tan / Inga Sandrock / Ivan Odak / Yuval Aizenbud / Anneke Wilharm / Joana Barros-Martins / Yaara Tabib / Alina Borchers / Tiago Amado / Lahiru Gangoda / Marco J. Herold / Marc Schmidt-Supprian / Jan Kisielow / Bruno Silva-Santos / Christian Koenecke / Avi-Hai Hovav / Christian Krebs / Immo Prinz / Sarina Ravens

    Cell Reports, Vol 27, Iss 12, Pp 3657-3671.e

    2019  Volume 4

    Abstract: Summary: IL-17-producing γδ T cells express oligoclonal Vγ4+ and Vγ6+ TCRs, mainly develop in the prenatal thymus, and later persist as long-lived self-renewing cells in all kinds of tissues. However, their exchange between tissues and the mechanisms of ... ...

    Abstract Summary: IL-17-producing γδ T cells express oligoclonal Vγ4+ and Vγ6+ TCRs, mainly develop in the prenatal thymus, and later persist as long-lived self-renewing cells in all kinds of tissues. However, their exchange between tissues and the mechanisms of their tissue-specific adaptation remain poorly understood. Here, single-cell RNA-seq profiling identifies IL-17-producing Vγ6+ T cells as a highly homogeneous Scart1+ population in contrast to their Scart2+ IL-17-producing Vγ4+ T cell counterparts. Parabiosis demonstrates that Vγ6+ T cells are fairly tissue resident in the thymus, peripheral lymph nodes, and skin. There, Scart1+ Vγ6+ T cells display tissue-specific gene expression signatures in the skin, characterized by steady-state production of the cytokines IL-17A and amphiregulin as well as by high expression of the anti-apoptotic Bcl2a1 protein family. Together, this study demonstrates how Scart1+ Vγ6+ T cells undergo tissue-specific functional adaptation to persist as effector cells in their skin habitat. : Tan et al. apply single-cell transcriptome analysis of tissue-resident Vγ6+ T cells and identify molecular determinants that mediate the functional adaptation and longevity of Scart1+ Vγ6+ T cells within tissues. Keywords: IL-17-producing γδ T cells, single-cell transcriptomics, tissue-resident γδ T cells, Vγ6+ T cells, Scart1, Scart2
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2019-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Shift of graft-versus-host-disease target organ tropism by dietary vitamin A.

    Christian Koenecke / Immo Prinz / Anja Bubke / Alina Schreder / Chun-Wei Lee / Oliver Pabst / Reinhold Förster

    PLoS ONE, Vol 7, Iss 5, p e

    2012  Volume 38252

    Abstract: Gut-homing of donor T cells is causative for the development of intestinal GvHD in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Expression of the gut-specific homing receptors integrin-α4β7 and chemokine receptor CCR9 on T ... ...

    Abstract Gut-homing of donor T cells is causative for the development of intestinal GvHD in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Expression of the gut-specific homing receptors integrin-α4β7 and chemokine receptor CCR9 on T cells is imprinted in gut-associated lymphoid tissues (GALT) under the influence of the vitamin A metabolite retinoic acid. Here we addressed the role of vitamin A deficiency in HSCT-recipients for donor T cell migration in the course of experimental GvHD. Vitamin A-deficient (VAD) mice were prepared by feeding them a vitamin A-depleted diet. Experiments were performed in a C57BL/6 into BALB/c model of acute GvHD. We found that expression of integrin-α4β7 and CCR9 in GALT was reduced in VAD recipients after HSCT. Competitive in vivo homing assays showed that allogeneic T cells primed in VAD mice did not home as efficiently to the intestine as T cells primed in mice fed with standard diet (STD). The course of GvHD was ameliorated in VAD HSCT-recipients and, consequently, their survival was prolonged compared to recipients receiving STD. However, VAD-recipients were not protected and died of clinical GvHD. We found reduced numbers of donor T cells in the intestine but increased cell counts and tissue damage in other organs of VAD-recipients. Furthermore, we observed high IFN-γ(+)CD4(+) and low FoxP3(+)CD4(+) frequencies of total donor CD4(+) T cells in VAD as compared to STD recipients. Taken together, these results indicate that dietary vitamin A deficiency in HSCT-recipients changed target organ tropism in GvHD but also resulted in fatal inflammation after HSCT.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Complications of Autologous Stem Cell Transplantation in Multiple Myeloma

    Anna Waszczuk-Gajda / Olaf Penack / Giulia Sbianchi / Linda Koster / Didier Blaise / Péter Reményi / Nigel Russell / Per Ljungman / Marek Trneny / Jiri Mayer / Simona Iacobelli / Guido Kobbe / Christof Scheid / Jane Apperley / Cyrille Touzeau / Stig Lenhoff / Esa Jantunen / Achilles Anagnostopoulos / Laura Paris /
    Paul Browne / Catherine Thieblemont / Nicolaas Schaap / Jorge Sierra / Ibrahim Yakoub-Agha / Laurent Garderet / Jan Styczynski / Helene Schoemans / Ivan Moiseev / Rafael F. Duarte / Zinaida Peric / Silvia Montoto / Anja van Biezen / Malgorzata Mikulska / Mahmoud Aljurf / Tapani Ruutu / Nicolaus Kröger / Curly Morris / Christian Koenecke / Stefan Schoenland / Grzegorz W. Basak

    Journal of Clinical Medicine, Vol 11, Iss 3541, p

    Results from the CALM Study

    2022  Volume 3541

    Abstract: Background: The main goal of this post hoc analysis of the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study was to evaluate the rate of short- and long-term infectious and non-infectious complications occurring ...

    Abstract Background: The main goal of this post hoc analysis of the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study was to evaluate the rate of short- and long-term infectious and non-infectious complications occurring after ASCT in patients with multiple myeloma (MM). Methods: The analysis included all patients with MM from the CALM study who underwent ≥1 ASCT. The primary endpoint of the analysis was to determine the rate of infectious and non-infectious complications after ASCT and to compare them in three time periods: 0–100 days, 101 days–1 year, and >1 year after the first transplant. Results: The analysis included a total of 3552 patients followed up for a median of 56.7 months (range 0.4–108.1). Complication rates decreased with the time from ASCT with 24.85 cases per 100 patient-years from day 0 to 100 days after the transplant, and <2.31 cases per 100 patient-years from the 101st day. At 100 days after ASC T, 45.7% of patients had complications, with infectious events being twice as frequent as non-infectious complications. Bacterial infections (6.5 cases per 100 patient-years, 95% CI: 6.1–7.0) and gastrointestinal complications (4.7 cases per 100 patient-years, 95% CI: 4.3–5.1) were the most common early events. The pattern of complications changed with time from ASCT. The presence of complications after ASCT was not associated with overall survival. Conclusions: Our data provide a solid basis for comparing ASCT-related complications to those caused by emerging treatments in multiple myeloma, such as CAR T-cell therapy and other immunotherapies.
    Keywords autologous stem cell transplantation in multiple myeloma ; complications ; multiple myeloma ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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