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CXCR5+CD4+ follicular helper T cells accumulate in resting human lymph nodes and have superior B cell helper activity

Havenith, Simone H. C. ; Remmerswaal, Ester B. M. ; Idu, Mirza M. ; [et al.]

Oxford University Press (OUP) ; 2014

In: International Immunology Vol. 26, No. 3 ( 2014-03-01), p. 183-192

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In: International Immunology, Oxford University Press (OUP), Vol. 26, No. 3 ( 2014-03-01), p. 183-192

Abstract: Although many relevant immune reactions are initiated in the lymph nodes, this compartment has not been systematically studied in humans. Analyses have been performed on immune cells derived from tonsils, but as this tissue is most often inflamed, generalization of these data is difficult. Here, we analyzed the phenotype and function of the human CD4+ T-cell subsets and lineages in paired resting lymph node and peripheral blood samples. Naive, central memory cells and effector memory cells as well as Th1, Th2, Th17 and Treg cells were equally represented in both compartments. On the other hand, cytotoxic CD4+ T cells were strikingly absent in the lymph nodes. CXCR5+CD4+ T cells, representing putative follicular Th (Tfh) cells were over-represented in lymph nodes and expressed higher levels of Tfh markers than their peripheral blood counterparts. Compared with the circulating pool, lymph-node-derived CXCR5+CD4+ T cells were superior in providing help to B cells. Thus, functionally competent Tfh cells accumulate in resting human lymph nodes, providing a swift induction of naive and memory antibody responses upon antigenic challenge.

Type of Medium: Online Resource

ISSN: 1460-2377 , 0953-8178

URL: Article

DOI: 10.1093/intimm/dxt058

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2014

detail.hit.zdb_id: 1467474-9

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Clonal Evolution of CD8 + T Cell Responses against Latent Viruses: Relationship among Phenotype, Localization, and Function

Remmerswaal, Ester B. M. ; Klarenbeek, Paul L. ; Alves, Nuno L. ; [et al.]

American Society for Microbiology ; 2015

In: Journal of Virology Vol. 89, No. 1 ( 2015-01), p. 568-580

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In: Journal of Virology, American Society for Microbiology, Vol. 89, No. 1 ( 2015-01), p. 568-580

Abstract: Human cytomegalovirus (hCMV) infection is characterized by a vast expansion of resting effector-type virus-specific T cells in the circulation. In mice, interleukin-7 receptor α (IL-7Rα)-expressing cells contain the precursors for long-lived antigen-experienced CD8 + T cells, but it is unclear if similar mechanisms operate to maintain these pools in humans. Here, we studied whether IL-7Rα-expressing cells obtained from peripheral blood (PB) or lymph nodes (LNs) sustain the circulating effector-type hCMV-specific pool. Using flow cytometry and functional assays, we found that the IL-7Rα + hCMV-specific T cell population comprises cells that have a memory phenotype and lack effector features. We used next-generation sequencing of the T cell receptor to compare the clonal repertoires of IL-7Rα + and IL-7Rα − subsets. We observed limited overlap of clones between these subsets during acute infection and after 1 year. When we compared the hCMV-specific repertoire between PB and paired LNs, we found many identical clones but also clones that were exclusively found in either compartment. New clones that were found in PB during antigenic recall were only rarely identical to the unique LN clones. Thus, although PB IL-7Rα-expressing and LN hCMV-specific CD8 + T cells show typical traits of memory-type cells, these populations do not seem to contain the precursors for the novel hCMV-specific CD8 + T cell pool during latency or upon antigen recall. IL-7Rα + PB and LN hCMV-specific memory cells form separate virus-specific compartments, and precursors for these novel PB hCMV-specific CD8 + effector-type T cells are possibly located in other secondary lymphoid tissues or are being recruited from the naive CD8 + T cell pool. IMPORTANCE Insight into the self-renewal properties of long-lived memory CD8 + T cells and their location is crucial for the development of both passive and active vaccination strategies. Human CMV infection is characterized by a vast expansion of resting effector-type cells. It is, however, not known how this population is maintained. We here investigated two possible compartments for effector-type cell precursors: circulating acute-phase IL-7Rα-expressing hCMV-specific CD8 + T cells and lymph node (LN)-residing hCMV-specific (central) memory cells. We show that new clones that appear after primary hCMV infection or during hCMV reactivation seldom originate from either compartment. Thus, although identical clones may be maintained by either memory population, the precursors of the novel clones are probably located in other (secondary) lymphoid tissues or are recruited from the naive CD8 + T cell pool.

Type of Medium: Online Resource

ISSN: 0022-538X , 1098-5514

URL: Article

DOI: 10.1128/JVI.02003-14

Language: English

Publisher: American Society for Microbiology

Publication Date: 2015

detail.hit.zdb_id: 1495529-5

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Human virus-specific effector-type T cells accumulate in blood but not in lymph nodes

Remmerswaal, Ester B. M. ; Havenith, Simone H. C. ; Idu, Mirza M. ; [et al.]

American Society of Hematology ; 2012

In: Blood Vol. 119, No. 7 ( 2012-02-16), p. 1702-1712

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In: Blood, American Society of Hematology, Vol. 119, No. 7 ( 2012-02-16), p. 1702-1712

Abstract: It is believed that the size of the CD8+ T-cell pool is fixed and that with every new viral challenge, the size of the pre-existing memory-cell population shrinks to make way for the new virus-specific cells. CMV-seropositive individuals have high numbers of CMV-specific resting-effector type CD8+ T cells in their peripheral blood (PB). This prompted us to investigate whether CMV infection limits immunologic space at sites where immune reactions are initiated, such as in the lymph nodes (LNs). LN and paired PB samples were analyzed for CMV-, EBV-, and influenza-specific CD8+ T cells. In marked contrast to blood, LNs contained significantly lower numbers of CX3CR1-expressing effector-type CD8+ T cells, whereas the CMV-specific cells that were found in the LNs resembled polyfunctional memory-type cells. In contrast, EBV- and influenza-specific CD8+ T cells were highly similar between PB and LNs both in number and function. Therefore, it is unlikely that CMV-specific CD8+ T cells in the LNs restrain the immunologic space of other virus-specific cells.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2011-09-381574

RVK:

XA 33000

RVK:

XA 10000

Language: English

Publisher: American Society of Hematology

Publication Date: 2012

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

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Quantitative analysis of mRNA-1273 COVID-19 vaccination response in immunocompromised adult hematology patients

Haggenburg, Sabine ; Lissenberg-Witte, Birgit I. ; van Binnendijk, Rob S. ; [et al.]

American Society of Hematology ; 2022

In: Blood Advances Vol. 6, No. 5 ( 2022-03-8), p. 1537-1546

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In: Blood Advances, American Society of Hematology, Vol. 6, No. 5 ( 2022-03-8), p. 1537-1546

Abstract: Vaccination guidelines for patients treated for hematological diseases are typically conservative. Given their high risk for severe COVID-19, it is important to identify those patients that benefit from vaccination. We prospectively quantified serum immunoglobulin G (IgG) antibodies to spike subunit 1 (S1) antigens during and after 2-dose mRNA-1273 (Spikevax/Moderna) vaccination in hematology patients. Obtaining S1 IgG ≥ 300 binding antibody units (BAUs)/mL was considered adequate as it represents the lower level of S1 IgG concentration obtained in healthy individuals, and it correlates with potent virus neutralization. Selected patients (n = 723) were severely immunocompromised owing to their disease or treatment thereof. Nevertheless, & gt;50% of patients obtained S1 IgG ≥ 300 BAUs/mL after 2-dose mRNA-1273. All patients with sickle cell disease or chronic myeloid leukemia obtained adequate antibody concentrations. Around 70% of patients with chronic graft-versus-host disease (cGVHD), multiple myeloma, or untreated chronic lymphocytic leukemia (CLL) obtained S1 IgG ≥ 300 BAUs/mL. Ruxolitinib or hypomethylating therapy but not high-dose chemotherapy blunted responses in myeloid malignancies. Responses in patients with lymphoma, patients with CLL on ibrutinib, and chimeric antigen receptor T-cell recipients were low. The minimal time interval after autologous hematopoietic cell transplantation (HCT) to reach adequate concentrations was & lt;2 months for multiple myeloma, 8 months for lymphoma, and 4 to 6 months after allogeneic HCT. Serum IgG4, absolute B- and natural killer–cell number, and number of immunosuppressants predicted S1 IgG ≥ 300 BAUs/mL. Hematology patients on chemotherapy, shortly after HCT, or with cGVHD should not be precluded from vaccination. This trial was registered at Netherlands Trial Register as #NL9553.

Type of Medium: Online Resource

ISSN: 2473-9529 , 2473-9537

URL: Article

DOI: 10.1182/bloodadvances.2021006917

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 2876449-3

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Expression and Function of S100A8/A9 (Calprotectin) in Human Typhoid Fever and the Murine Salmonella Model

De Jong, Hanna K. ; Achouiti, Ahmed ; Koh, Gavin C. K. W. ; [et al.]

Public Library of Science (PLoS) ; 2015

In: PLOS Neglected Tropical Diseases Vol. 9, No. 4 ( 2015-4-10), p. e0003663-

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In: PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 9, No. 4 ( 2015-4-10), p. e0003663-

Type of Medium: Online Resource

ISSN: 1935-2735

URL: Article

DOI: 10.1371/journal.pntd.0003663

DOI: 10.1371/journal.pntd.0003663.g001

DOI: 10.1371/journal.pntd.0003663.g002

DOI: 10.1371/journal.pntd.0003663.g003

DOI: 10.1371/journal.pntd.0003663.g004

DOI: 10.1371/journal.pntd.0003663.g005

DOI: 10.1371/journal.pntd.0003663.g006

DOI: 10.1371/journal.pntd.0003663.t001

DOI: 10.1371/journal.pntd.0003663.t002

DOI: 10.1371/journal.pntd.0003663.s001

DOI: 10.1371/journal.pntd.0003663.s002

DOI: 10.1371/journal.pntd.0003663.s003

DOI: 10.1371/journal.pntd.0003663.s004

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2015

detail.hit.zdb_id: 2429704-5

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Human intrahepatic CD69 + CD8+ T cells have a tissue resident memory T cell phenotype with reduced cytolytic capacity

Stelma, Femke ; de Niet, Annikki ; Sinnige, Marjan J. ; [et al.]

Springer Science and Business Media LLC ; 2017

In: Scientific Reports Vol. 7, No. 1 ( 2017-07-21)

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In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-07-21)

Abstract: Tissue resident memory T cells (T RM ) have been identified in various tissues, however human liver T RM to date remain unidentified. T RM can be recognized by CD69 and/or CD103 expression and may play a role in the pathology of chronic hepatitis B (CHB) and hepatitis C virus infection (CHC). Liver and paired blood mononuclear cells from 17 patients (including 4 CHB and 6 CHC patients) were isolated and CD8+ T cells were comprehensively analysed by flowcytometry, immunohistochemistry and qPCR. The majority of intrahepatic CD8+ T cells expressed CD69, a marker used to identify T RM , of which a subset co-expressed CD103. CD69 + CD8+ T cells expressed low levels of S1PR1 and KLF2 and a large proportion ( 〉 90%) was CXCR6+, resembling liver T RM in mice and liver resident NK cells in human. Cytotoxic proteins were only expressed in a small fraction of liver CD69 + CD8+ T cells in patients without viral hepatitis, however, in livers from CHB patients more CD69 + CD8+ T cells were granzyme B+. In CHC patients, less intrahepatic CD69 + CD8+ T cells were Hobit+ as compared to CHB and control patients. Intrahepatic CD69 + CD8+ T cells likely T RM which have a reduced cytolytic potential. In patients with chronic viral hepatitis T RM have a distinct phenotype.

Type of Medium: Online Resource

ISSN: 2045-2322

URL: Article

DOI: 10.1038/s41598-017-06352-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2017

detail.hit.zdb_id: 2615211-3

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Immunogenicity of the Currently Recommended Pneumococcal Vaccination Schedule in Patients With Inflammatory Bowel Disease

van Aalst, Mariëlle ; Garcia Garrido, Hannah M ; van der Leun, Josephine ; [et al.]

Oxford University Press (OUP) ; 2019

In: Clinical Infectious Diseases ( 2019-03-22)

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In: Clinical Infectious Diseases, Oxford University Press (OUP), ( 2019-03-22)

Abstract: Patients with inflammatory bowel disease (IBD) are at increased risk of invasive pneumococcal infections. Therefore, vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) 2 months later is recommended. However, the level of immunogenicity induced by this vaccination schedule in IBD patients with and without immunosuppressive medication remains unclear. Methods We prospectively assessed the immunogenicity of PCV13 followed by PPSV23 in IBD patients by measuring serotype-specific pneumococcal immunoglobulin G antibody concentrations at baseline and 4–8 weeks postvaccination. Response to vaccination was defined as a postvaccination antibody concentration ≥1.3 μg/mL for 70% of the measured serotypes. We analyzed the immunogenic effect of 4 different medication regimens: (1) conventional immunomodulators (ie, oral prednisolone 〉 10 mg/day, thiopurines, methotrexate); (2) anti–tumor necrosis factor agents; (3) combination therapy; and (4) no treatment with immunosuppressive agents (control group). Results One hundred forty-one IBD patients were included, of whom 37 were controls. Adequate response to vaccination was 59% (61/104) in patients using immunosuppressive agents (groups 1–3) vs 81% (30/37) in controls (odds ratio, 0.33 [95% confidence interval, .13–.82]). A combination of different immunosuppressive drugs most severely impaired the immune response to pneumococcal vaccination (response, 52% [15/29] ). Conclusions Although the sequential vaccination schedule of PCV13 followed by PPSV23 is safe, immunogenic, and thus beneficial in the majority of IBD patients, those receiving immunosuppressive agents, and especially those receiving combination therapy, have an impaired immune response compared to controls. Therefore, preferably, vaccinations should be administered before the initiation of immunosuppressive therapy.

Type of Medium: Online Resource

ISSN: 1058-4838 , 1537-6591

URL: Article

DOI: 10.1093/cid/ciz226

RVK:

XA 10000

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2019

detail.hit.zdb_id: 2002229-3

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OptimisAtion of Diagnostic Accuracy in idioPathic inflammaTory myopathies (ADAPT study): a protocol for a prospective diagnostic accuracy study of multimodality testing in patients suspected of a treatable idiopathic inflammatory myopathy

Walter, Hannah A W ; Kamperman, Renske G ; Raaphorst, Joost ; [et al.]

BMJ ; 2021

In: BMJ Open Vol. 11, No. 12 ( 2021-12), p. e053594-

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In: BMJ Open, BMJ, Vol. 11, No. 12 ( 2021-12), p. e053594-

Abstract: Idiopathic inflammatory myopathies (IIMs) excluding inclusion body myositis (IBM) are a group of heterogeneous autoimmune disorders characterised by subacute-onset and progressive proximal muscle weakness, which are frequently part of a multisystem autoimmune disorder. Reaching the diagnosis can be challenging, and no gold standard for the diagnosis of IIM exists. Diagnostic modalities include serum creatine kinase activity, muscle imaging (MRI or ultrasound (US)), electromyography (EMG), myositis autoantibody testing and muscle biopsy. Several diagnostic criteria have been developed for IIMs, varying in reported sensitivity and specificity. Hypothesis We hypothesise that an evidence-based diagnostic strategy, using fewer and preferably the least invasive diagnostic modalities, can achieve the accuracy of a complete panel of diagnostic tests, including MRI, US, EMG, myositis-specific autoantibody testing and muscle biopsy. Methods and analysis The OptimizAtion of Diagnostic Accuracy in idioPathic inflammaTory myopathies study is a prospective diagnostic accuracy study with an over-complete study design. 100 patients suspected of an IIM excluding IBM will be included. A reference diagnosis will be assigned by an expert panel using all clinical information and all results of all ancillary tests available, including 6 months of follow-up. Several predefined diagnostic strategies will be compared against the reference diagnosis to find the optimal diagnostic strategy. Ethics and dissemination Ethical approval was obtained from the medical ethics committee of the Academic Medical Centre, University of Amsterdam, The Netherlands (2019-814). The results will be distributed through conference presentations and peer-reviewed publications. Trial registration number Netherlands trial register; NL8764.

Type of Medium: Online Resource

ISSN: 2044-6055 , 2044-6055

URL: Article

DOI: 10.1136/bmjopen-2021-053594

Language: English

Publisher: BMJ

Publication Date: 2021

detail.hit.zdb_id: 2599832-8

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T-Cell Activation Independently Associates With Immune Senescence in HIV-Infected Recipients of Long-term Antiretroviral Treatment

AGEhIV Study Group ; Jiménez, Viviana Cobos ; Wit, Ferdinand W. N. M. ; [et al.]

Oxford University Press (OUP) ; 2016

In: The Journal of Infectious Diseases Vol. 214, No. 2 ( 2016-07-15), p. 216-225

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In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 214, No. 2 ( 2016-07-15), p. 216-225

Abstract: Background. Aging-associated noncommunicable comorbidities are more prevalent among human immunodeficiency virus type 1 (HIV)–infected individuals than among HIV-uninfected individuals. Residual HIV-related chronic immune activation and senescence may increase the risk of developing comorbidities. Methods. Immune phenotyping, thymic output, and telomere length were assessed in 94 HIV-infected individuals who were aged & gt;45 years and receiving antiretroviral therapy (ART; cases) and 95 age-matched uninfected controls. Results. Cases had lower CD4+ T-cell counts, higher CD8+ T-cell counts, and increased levels of immune activation (ie, increased soluble CD14 [sCD14] level and increased percentages of CD38+HLA-DR+ cells among both CD4+ and CD8+ T cells), regulatory T cells, and percentage of programmed cell death 1 (PD-1)–expressing cells among CD4+ T cells. Immune senescence levels (ie, percentages of CD27−CD28− cells or CD57+ cells) were comparable between cases and controls. Peripheral blood mononuclear cells from cases had shorter telomeres but increased single-joint T-cell receptor excision circle content and CD31+ naive CD4+ T cells. Although cytomegalovirus (CMV) antibody titers were higher in cases, CMV-specific T-cell responses were comparable between cases and controls. T-cell senescence in cases was independently associated with T-cell activation but not with CMV-specific immune responses. Conclusions. Despite long-term receipt of ART, HIV-infected adults had higher levels of immune activation, regulatory T cells, and PD-1–expressing CD4+ cells and shorter telomeres. The increased soluble CD14 levels and percentage of CD38+HLA-DR+ cells among CD4+ T cells correlated with shorter telomeres and increased regulatory T-cell levels. This suggests that HIV influences immune function irreversibly, with several pathways that are persistently abnormal during effective ART. Therapies aimed at improving immune health during ART are needed.

Type of Medium: Online Resource

ISSN: 0022-1899 , 1537-6613

URL: Article

DOI: 10.1093/infdis/jiw146

RVK:

XA 10000

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2016

detail.hit.zdb_id: 1473843-0

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Phenotypic and Functional Comparison of Class Switch Recombination Deficiencies with a Subgroup of Common Variable Immunodeficiencies

aan de Kerk, Daan J. ; Jansen, Machiel H. ; Jolles, Stephen ; [et al.]

Springer Science and Business Media LLC ; 2016

In: Journal of Clinical Immunology Vol. 36, No. 7 ( 2016-10), p. 656-666

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In: Journal of Clinical Immunology, Springer Science and Business Media LLC, Vol. 36, No. 7 ( 2016-10), p. 656-666

Type of Medium: Online Resource

ISSN: 0271-9142 , 1573-2592

URL: Article

DOI: 10.1007/s10875-016-0321-2

RVK:

XA 10000

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2016

detail.hit.zdb_id: 2016755-6

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