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Article: Immune defects in the risk of infection and response to vaccination in monoclonal gammopathy of undetermined significance and multiple myeloma.

Tete, Sarah M / Bijl, Marc / Sahota, Surinder S / Bos, Nicolaas A

2014 Volume 5, Page(s) 257

Abstract: The plasma cell proliferative disorders monoclonal gammopathy of undetermined significance (MGUS) and malignant multiple myeloma (MM) are characterized by an accumulation of transformed clonal plasma cells in the bone marrow and production of monoclonal ... ...

Abstract	The plasma cell proliferative disorders monoclonal gammopathy of undetermined significance (MGUS) and malignant multiple myeloma (MM) are characterized by an accumulation of transformed clonal plasma cells in the bone marrow and production of monoclonal immunoglobulin. They typically affect an older population, with median age of diagnosis of approximately 70 years. In both disorders, there is an increased risk of infection due to the immunosuppressive effects of disease and conjointly of therapy in MM, and response to vaccination to counter infection is compromised. The underlying factors in a weakened immune response in MGUS and MM are as yet not fully understood. A confounding factor is the onset of normal aging, which quantitatively and qualitatively hampers humoral immunity to affect response to infection and vaccination. In this review, we examine the status of immune alterations in MGUS and MM and set these against normal aging immune responses. We focus primarily on quantitative and functional aspects of B-cell immunity. Furthermore, we review the current knowledge relating to susceptibility to infectious disease in MGUS and MM, and how efficacy of conventional vaccination is affected by proliferative disease-related and therapy-related factors.
Language	English
Publishing date	2014-06-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2014.00257
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Article ; Online: Impact of pre-existing immunity on the induction of functional cross-reactive anti-hemagglutinin stalk antibodies following vaccination with an AS03 adjuvanted pandemic H1N1 vaccine.

Tete, Sarah M / Jul-Larsen, Åsne / Rostami, Sina / Lunde, Turid Helen Felli / Søland, Hanne / Krammer, Florian / Cox, Rebecca J

Vaccine

2018 Volume 36, Issue 16, Page(s) 2213–2219

Abstract: The 2009 pandemic H1N1 (A(H1N1)pdm09) virus had a highly divergent hemagglutinin (HA) compared to pre-2009 seasonal H1N1 strains. Most peoples were immunologically naïve to the A(H1N1)pdm09, although hospital workers were exposed early in the pandemic ... ...

Abstract	The 2009 pandemic H1N1 (A(H1N1)pdm09) virus had a highly divergent hemagglutinin (HA) compared to pre-2009 seasonal H1N1 strains. Most peoples were immunologically naïve to the A(H1N1)pdm09, although hospital workers were exposed early in the pandemic before pandemic vaccines became available. Here, we evaluated how pre-existing antibodies influence the induction of cross-functional HA stalk antibodies following A(H1N1)pdm09 vaccination. Fifty-six healthcare workers vaccinated with AS03 adjuvanted A(H1N1)pdm09 vaccine were chosen by their pre-vaccination priming status (primed HI titers ≥ 40 or unprimed < 40). We analyzed the HA head- and stalk-specific serum IgG subclasses at pre- and 21 days post-vaccination. We also assessed the functionality of the HA stalk-specific antibodies to neutralize virus and mediate antibody dependent cellular cytotoxicity (ADCC). Primed individuals had higher pre-existing HA head- and stalk-specific IgG1, as well as higher ADCC functionality of stalk antibodies. However, following vaccination with the adjuvanted pandemic vaccine, only the quantity of HA head specific IgG1 antibodies were significantly higher than in unprimed individuals. The priming status did not impact upon the cross-reactive HA stalk specific IgG antibodies or their ability to neutralize virus or induce ADCC post-vaccination. In conclusion, a single dose of AS03 adjuvanted pandemic vaccine elicited similar levels of functional antibodies in naïve and primed individuals. These findings are important for understanding the immunological factors that impact or modulate pandemic vaccine responses in humans.
MeSH term(s)	Adjuvants, Immunologic ; Adult ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Antibody-Dependent Cell Cytotoxicity/immunology ; Cross Reactions/immunology ; Female ; Health Personnel ; Hemagglutination Inhibition Tests ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Humans ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Immunologic Memory ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza Vaccines/administration & dosage ; Influenza Vaccines/immunology ; Influenza, Human/immunology ; Influenza, Human/prevention & control ; Male ; Middle Aged ; Public Health Surveillance ; Vaccination
Chemical Substances	Adjuvants, Immunologic ; Antibodies, Neutralizing ; Antibodies, Viral ; Hemagglutinin Glycoproteins, Influenza Virus ; Immunoglobulin G ; Influenza Vaccines
Language	English
Publishing date	2018-03-13
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2018.02.022
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Article: Impact of pre-existing immunity on the induction of functional cross-reactive anti-hemagglutinin stalk antibodies following vaccination with an AS03 adjuvanted pandemic H1N1 vaccine

Tete, Sarah M / Cox, Rebecca J / Jul-Larsen, Åsne / Krammer, Florian / Lunde, Turid Helen Felli / Rostami, Sina / Søland, Hanne

Vaccine. 2018 Apr. 12, v. 36, no. 16

2018

Abstract	The 2009 pandemic H1N1 (A(H1N1)pdm09) virus had a highly divergent hemagglutinin (HA) compared to pre-2009 seasonal H1N1 strains. Most peoples were immunologically naïve to the A(H1N1)pdm09, although hospital workers were exposed early in the pandemic before pandemic vaccines became available. Here, we evaluated how pre-existing antibodies influence the induction of cross-functional HA stalk antibodies following A(H1N1)pdm09 vaccination.Fifty-six healthcare workers vaccinated with AS03 adjuvanted A(H1N1)pdm09 vaccine were chosen by their pre-vaccination priming status (primed HI titers ≥ 40 or unprimed < 40). We analyzed the HA head- and stalk-specific serum IgG subclasses at pre- and 21 days post-vaccination. We also assessed the functionality of the HA stalk-specific antibodies to neutralize virus and mediate antibody dependent cellular cytotoxicity (ADCC).Primed individuals had higher pre-existing HA head- and stalk-specific IgG1, as well as higher ADCC functionality of stalk antibodies. However, following vaccination with the adjuvanted pandemic vaccine, only the quantity of HA head specific IgG1 antibodies were significantly higher than in unprimed individuals. The priming status did not impact upon the cross-reactive HA stalk specific IgG antibodies or their ability to neutralize virus or induce ADCC post-vaccination. In conclusion, a single dose of AS03 adjuvanted pandemic vaccine elicited similar levels of functional antibodies in naïve and primed individuals. These findings are important for understanding the immunological factors that impact or modulate pandemic vaccine responses in humans.
Keywords	antibodies ; blood serum ; cytotoxicity ; health care workers ; hemagglutinins ; humans ; immunity ; immunoglobulin G ; neutralization ; pandemic ; vaccination ; vaccines ; viruses
Language	English
Dates of publication	2018-0412
Size	p. 2213-2219.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2018.02.022
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Article ; Online: Comparative analysis of influenza A(H3N2) virus hemagglutinin specific IgG subclass and IgA responses in children and adults after influenza vaccination.

Manenti, Alessandro / Tete, Sarah M / Mohn, Kristin G-I / Jul-Larsen, Åsne / Gianchecchi, Elena / Montomoli, Emanuele / Brokstad, Karl A / Cox, Rebecca J

Vaccine

2017 Volume 35, Issue 1, Page(s) 191–198

Abstract: Two different influenza vaccines are generally used in many countries; trivalent live attenuated influenza vaccine (LAIV3) and trivalent inactivated influenza vaccine (IIV3). Studies comparing the antibody response to IIV3 and LAIV3 commonly investigate ... ...

Abstract	Two different influenza vaccines are generally used in many countries; trivalent live attenuated influenza vaccine (LAIV3) and trivalent inactivated influenza vaccine (IIV3). Studies comparing the antibody response to IIV3 and LAIV3 commonly investigate the seroprotective response by hemagglutination-inhibition (HI) assay. However, there is limited data regarding comparative analysis of IgG subclass and IgA responses induced by LAIV3 and IIV3. Fifteen children <5years received 2 doses of LAIV3 while 14 children aged 10-17years received one dose. In addition, 15 adults were vaccinated with either intranasal LAIV3 or intramuscular IIV3. We analyzed the H3N2 humoral responses by HI assay and the hemagglutinin (HA) specific IgG1, IgG2, IgG3, IgG4 and IgA1 responses by ELISA. Furthermore, we investigated the avidity of induced IgG antibodies. Pre-existing seroprotective HI antibodies were present in adults (73%) previously vaccinated with IIV3. Vaccination resulted in a significant increase in HI titers in all groups, except LAIV3 vaccinated adults. Furthermore, a negative correlation between age and HI titers in LAIV3 vaccinated subjects was observed post-vaccination. LAIV3 in children and IIV3 in adults induced HA-specific IgG1, low IgG3 but no IgG2 or IgG4. Moreover, significant IgA1 responses were only induced in children. Interestingly, IIV3 and LAIV3 induced IgG antibodies with comparable and significantly augmented avidity post-vaccination in children and adults. Our results suggest that age and/or exposure history play a significant role in determining the antibody response. Clinical trial registry: ClinicalTrials.gov NCT01003288 and NCT01866540.
Language	English
Publishing date	2017-01-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2016.10.024
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Article: Dissecting the hemagglutinin head and stalk-specific IgG antibody response in healthcare workers following pandemic H1N1 vaccination.

Tete, Sarah M / Krammer, Florian / Lartey, Sarah / Bredholt, Geir / Wood, John / Skrede, Steinar / Cox, Rebecca J

NPJ vaccines

2016 Volume 1

Abstract: Traditionally, neutralising antibodies that are directed to the major surface glycoprotein hemagglutinin (HA) head domain are measured as surrogate correlates of protection against influenza. In addition to neutralization, hemagglutinin-specific ... ...

Abstract	Traditionally, neutralising antibodies that are directed to the major surface glycoprotein hemagglutinin (HA) head domain are measured as surrogate correlates of protection against influenza. In addition to neutralization, hemagglutinin-specific antibodies may provide protection by mediating antibody-dependent cellular cytotoxicity (ADCC). During the 2009 pandemic, vaccination induced HA-specific antibodies that were mostly directed to the conserved HA stalk domain. However, the protective role of these antibodies has not been investigated in detail. We quantified the HA head and stalk-specific antibodies, their avidity, ability to neutralise virus and activate natural killer cells in an ADCC assay. We analyzed sera obtained from 14 healthcare workers who had low hemagglutination inhibition (HI) antibody titres at 3 months after pandemic H1N1 vaccination as well as from 22 controls. Vaccination resulted in a HA stalk dominant antibody response in both low responders and controls. Revaccination of low responders, 5 months later, resulted in a boost in antibodies, with HA head-specific antibodies dominating the response. Comparative analysis of head and stalk antibody avidities revealed that stalk-specific antibodies were qualitatively superior. Furthermore, stalk-specific antibodies mediated virus neutralization and had significantly higher ADCC activity than head-specific antibodies. Despite the head and stalk-specific antibodies being lower in low responders, they had comparable antibody avidity, ADCC functionality and neutralising capacity to those of controls who had high HI titres post-vaccination. Thus, our study has demonstrated that HA stalk-specific antibodies may have an important role in protection through neutralization and ADCC in low responders who do not maintain seroprotective HI antibodies.
Language	English
Publishing date	2016-07-28
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN	2059-0105
DOI	10.1038/npjvaccines.2016.1
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Article ; Online: Monoclonal paraprotein influences baseline B-cell repertoire diversity and perturbates influenza vaccination-induced B-cell response.

Tete, Sarah M / Kipling, David / Westra, Johanna / de Haan, Aalzen / Bijl, Marc / Dunn-Walters, Deborah K / Sahota, Surinder S / Bos, Nicolaas A

Experimental hematology

2015 Volume 43, Issue 6, Page(s) 439–47.e1

Abstract: Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasma cells in the bone marrow, secreting monoclonal (M) paraprotein. It is associated with increased susceptibility to infections, which may reflect altered B- ... ...

Abstract	Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasma cells in the bone marrow, secreting monoclonal (M) paraprotein. It is associated with increased susceptibility to infections, which may reflect altered B-cell repertoire. To investigate this, we examined the immunoglobulin (Ig) M, IgG, and IgA B-cell repertoire diversity in MGUS at baseline and after influenza vaccination (n = 16) in comparison with healthy controls (HCs; n = 16). The Complementary Determining Region 3 region of the immunoglobulin heavy chain variable region gene was amplified and B-cell spectratypes analyzed by high-resolution electrophoresis. Spectratype Gaussian distribution, kurtosis, and skewness were quantified to measure repertoire shifts. Both HC and MGUS baseline spectratypes show interindividual variability that is more pronounced in the IGHG and IGHA repertoires. Overall, baseline B-cell repertoire is more altered in MGUS, with oligoclonality observed in 50% (p = 0.01). Postvaccination, significant differences emerged in MGUS in relation to M-protein levels. High M-protein concentration is associated with a more oligoclonal IgG and IgA response at day 7 postvaccination, and, in contrast to HCs, vaccination also induced significant perturbations in the MGUS IgM repertoire at day 7 (p = 0.005). Monoclonal expansion in MGUS thus has an effect on the baseline B-cell repertoire and influences the recruited repertoire upon vaccination.
MeSH term(s)	Aged ; Aged, 80 and over ; B-Lymphocytes/immunology ; Base Sequence ; DNA Primers ; Female ; Humans ; Immunoglobulin Heavy Chains/immunology ; Influenza Vaccines/administration & dosage ; Influenza Vaccines/immunology ; Male ; Middle Aged ; Monoclonal Gammopathy of Undetermined Significance/immunology ; Paraproteins/physiology ; Polymerase Chain Reaction
Chemical Substances	DNA Primers ; Immunoglobulin Heavy Chains ; Influenza Vaccines ; Paraproteins
Language	English
Publishing date	2015-03-18
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	185107-x
ISSN	1873-2399 ; 0531-5573 ; 0301-472X
ISSN (online)	1873-2399
ISSN	0531-5573 ; 0301-472X
DOI	10.1016/j.exphem.2015.02.005
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Article ; Online: Persistence and avidity maturation of antibodies to A(H1N1)pdm09 in healthcare workers following repeated annual vaccinations.

Eidem, Synnøve / Tete, Sarah M / Jul-Larsen, Åsne / Hoschler, Katja / Montomoli, Emanuele / Brokstad, Karl A / Cox, Rebecca J

Vaccine

2015 Volume 33, Issue 33, Page(s) 4146–4154

Abstract: Healthcare workers are at increased risk of influenza infection through direct patient care, particularly during the early stages of a pandemic. Although influenza vaccination is widely recommended in Healthcare workers, data on long-term immunogenicity ... ...

Abstract	Healthcare workers are at increased risk of influenza infection through direct patient care, particularly during the early stages of a pandemic. Although influenza vaccination is widely recommended in Healthcare workers, data on long-term immunogenicity of vaccination in healthcare workers are lacking. The present study was designed to assess the persistence of the humoral response after pandemic vaccination as well as the impact of repeated annual vaccination in healthcare workers (n=24). Pandemic influenza vaccination resulted in a significant increase in haemagglutination inhibition (HI) antibody titers with 93-100% of subjects achieving protective titers 21-days post each of the three annual vaccinations. Seroprotective antibodies measured by HI, microneutralization and single radial hemolysis assays were present in 77-94% of healthcare workers 6 months post-vaccination. Repeated vaccination resulted in an increased duration of seroprotective antibodies with seroprotective titers increasing from 35-62% 12 months after 2009 pandemic vaccination to 50-75% 12 months after 2010 vaccination. Furthermore, repeated annual vaccination augmented the avidity of influenza-specific IgG antibodies. In conclusion, we have shown that A(H1N1)pdm09 vaccination induces high seroprotective titers that persist for at least 6 months. We demonstrate that repeated vaccination is beneficial to healthcare workers and results in further avidity maturation of vaccine-induced antibodies.
MeSH term(s)	Adult ; Antibodies, Viral/blood ; Antibody Affinity ; Health Personnel ; Hemagglutination Inhibition Tests ; Humans ; Immunodiffusion ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza Vaccines/administration & dosage ; Influenza Vaccines/immunology ; Middle Aged ; Neutralization Tests ; Young Adult
Chemical Substances	Antibodies, Viral ; Influenza Vaccines
Language	English
Publishing date	2015-08-07
Publishing country	Netherlands
Document type	Clinical Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2015.05.081
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Article ; Online: Influenza A haemagglutinin specific IgG responses in children and adults after seasonal trivalent live attenuated influenza vaccination.

Islam, Shahinul / Mohn, Kristin Greve-Isdahl / Krammer, Florian / Sanne, Mari / Bredholt, Geir / Jul-Larsen, Åsne / Tete, Sarah M / Zhou, Fan / Brokstad, Karl Albert / Cox, Rebecca Jane

Vaccine

2017 Volume 35, Issue 42, Page(s) 5666–5673

Abstract: Influenza is a major respiratory pathogen and vaccination is the main method of prophylaxis. In 2012, the trivalent live attenuated influenza vaccine (LAIV3) was licensed in Europe for use in children. Vaccine-induced antibodies directed against the main ...

Abstract	Influenza is a major respiratory pathogen and vaccination is the main method of prophylaxis. In 2012, the trivalent live attenuated influenza vaccine (LAIV3) was licensed in Europe for use in children. Vaccine-induced antibodies directed against the main viral surface glycoprotein, haemagglutinin (HA), play an important role in virus neutralization through different mechanism. The objective of this study was to dissect the HA specific antibody responses induced after LAIV3 immunization to the influenza A viruses in children and adults. Plasma was collected from 20 children and 20 adults pre- and post-LAIV3 vaccination (up to ayear) and analysed by the haemagglutination inhibition (HI) and ELISA assays. We found that LAIV3 boosted the HA specific IgG response against the head and the full-length of H3N2 in children, but not adults. Adults had higher levels of pre-existing stalk antibodies (towards H3N2 and H1N1), but these were not boosted by LAIV3. Importantly, we observed a trend in boosting of H1N1 HA stalk specific antibodies in children after LAIV3. Whereas, heterosubtypic H5 and H7 full-length HA specific antibodies were not boosted in either children or adults. In conclusion, LAIV3 elicited H3-head and low levels of H1 stalk specific antibody responses in children, supporting the prophylactic use of LAIV in children.
Language	English
Publishing date	2017-10-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2017.08.044
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Article ; Online: Aging disturbs the balance between effector and regulatory CD4+ T cells.

van der Geest, Kornelis S M / Abdulahad, Wayel H / Tete, Sarah M / Lorencetti, Pedro G / Horst, Gerda / Bos, Nicolaas A / Kroesen, Bart-Jan / Brouwer, Elisabeth / Boots, Annemieke M H

Experimental gerontology

2014 Volume 60, Page(s) 190–196

Abstract: Healthy aging requires an optimal balance between pro-inflammatory and anti-inflammatory immune responses. Although CD4+ T cells play an essential role in many immune responses, few studies have directly assessed the effect of aging on the balance ... ...

Abstract	Healthy aging requires an optimal balance between pro-inflammatory and anti-inflammatory immune responses. Although CD4+ T cells play an essential role in many immune responses, few studies have directly assessed the effect of aging on the balance between effector T (Teff) cells and regulatory T (Treg) cells. Here, we determined if and how aging affects the ratio between Treg and Teff cells. Percentages of both naive Treg (nTreg; CD45RA+CD25(int)FOXP3(low)) and memory Treg (memTreg; CD45RA-CD25(high)FOXP3(high)) cells were determined by flow cytometry in peripheral blood samples of healthy individuals of various ages (20-84 years). Circulating Th1, Th2 and Th17 effector cells were identified by intracellular staining for IFN-γ, IL-4 and IL-17, respectively, upon in vitro stimulation with PMA and calcium ionophore. Whereas proportions of nTreg cells declined with age, memTreg cells increased. Both Th1 and Th2 cells were largely maintained in the circulation of aged humans, whereas Th17 cells were decreased. Similar to memTreg cells, the 3 Teff subsets resided primarily in the memory CD4+ T cell compartment. Overall, Treg/Teff ratios were increased in the memory CD4+ T cell compartment of aged individuals when compared to that of young individuals. Finally, the relative increase of memTreg cells in elderly individuals was associated with poor responses to influenza vaccination. Taken together, our findings imply that aging disturbs the balance between Treg cells and Teff cells.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Aging/immunology ; CD4-Positive T-Lymphocytes/immunology ; Cohort Studies ; Female ; Humans ; Immunologic Memory ; Influenza Vaccines/administration & dosage ; Influenza Vaccines/immunology ; Male ; Middle Aged ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Regulatory/immunology ; Th1 Cells/immunology ; Th17 Cells/immunology ; Th2 Cells/immunology ; Young Adult
Chemical Substances	Influenza Vaccines
Language	English
Publishing date	2014-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	390992-x
ISSN	1873-6815 ; 0531-5565
ISSN (online)	1873-6815
ISSN	0531-5565
DOI	10.1016/j.exger.2014.11.005
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Article ; Online: Low-affinity TCR engagement drives IL-2-dependent post-thymic maintenance of naive CD4+ T cells in aged humans.

van der Geest, Kornelis S M / Abdulahad, Wayel H / Teteloshvili, Nato / Tete, Sarah M / Peters, Jorieke H / Horst, Gerda / Lorencetti, Pedro G / Bos, Nicolaas A / Lambeck, Annechien / Roozendaal, Caroline / Kroesen, Bart-Jan / Koenen, Hans J P M / Joosten, Irma / Brouwer, Elisabeth / Boots, Annemieke M H

Aging cell

2015 Volume 14, Issue 5, Page(s) 744–753

Abstract: Insight into the maintenance of naive T cells is essential to understand defective immune responses in the context of aging and other immune compromised states. In humans, naive CD4+ T cells, in contrast to CD8+ T cells, are remarkably well retained with ...

Abstract	Insight into the maintenance of naive T cells is essential to understand defective immune responses in the context of aging and other immune compromised states. In humans, naive CD4+ T cells, in contrast to CD8+ T cells, are remarkably well retained with aging. Here, we show that low-affinity TCR engagement is the main driving force behind the emergence and accumulation of naive-like CD4+ T cells with enhanced sensitivity to IL-2 in aged humans. In vitro, we show that these CD45RA(+) CD25(dim) CD4(+) T cells can develop from conventional naive CD25(-) CD4+ T cells upon CD3 cross-linking alone, in the absence of costimulation, rather than via stimulation by the homeostatic cytokines IL-2, IL-7, or IL-15. In vivo, TCR engagement likely occurs in secondary lymphoid organs as these cells were detected in lymph nodes and spleen where they showed signs of recent activation. CD45RA(+) CD25(dim) CD4+ T cells expressed a broad TCRVβ repertoire and could readily differentiate into functional T helper cells. Strikingly, no expansion of CD45RA(+) CD25(dim) CD8+ T cells was detected with aging, thereby implying that maintenance of naive CD4+ T cells is uniquely regulated. Our data provide novel insight into the homeostasis of naive T cells and may guide the development of therapies to preserve or restore immunity in the elderly.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Aging/blood ; Aging/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Cross-Sectional Studies ; Humans ; Interleukin-2/immunology ; Middle Aged ; Receptors, Antigen, T-Cell/immunology ; Thymus Gland/cytology ; Thymus Gland/immunology ; Young Adult
Chemical Substances	Interleukin-2 ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2015-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2113083-8
ISSN	1474-9726 ; 1474-9718
ISSN (online)	1474-9726
ISSN	1474-9718
DOI	10.1111/acel.12353
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