PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 11992271

Age-related decrease in adenovirus-specific T cell responses.

Martina Sester·Urban Sester·Susana Alarcon Salvador·Gunnar Heine·Sabine Lipfert·Matthias Girndt·Barbara Gärtner·Hans Köhler
View original source ↗Export metadata ↓

Abstract

Infections with persistent viruses, such as cytomegalovirus (CMV) or adenovirus, are not, in general, clinically apparent but may cause serious complications in the immunocompromised host. As has been shown for CMV, the cellular arm of the immune response is essential in controlling viral replication. However, cellular immunity toward adenoviruses has not been well characterized in humans. The aim of the present study was the quantitative and functional analysis of adenovirus-specific T cell responses from 171 healthy individuals and 59 long-term renal transplant recipients by use of flow-cytometric, as well as standard proliferation and enzyme-linked immunosorbant, assays. Adenovirus-specific immunity is dominated by CD4 T cells with memory/effector phenotype. Of interest, the frequency of adenovirus-specific T cells decreases significantly with age. This age-related decline indicates the eventual elimination of adenoviruses within a lifetime that may explain the well-known clinical observation of a predominant incidence of adenoviral complications in children and young adults, compared with older adults, after transplantation.

Explore related subjects

AdenoviridaeAdenoviridae InfectionsAdultAge FactorsAgedAged, 80 and overAntibodies, ViralCD4-Positive T-LymphocytesCytokinesEnzyme-Linked Immunosorbent AssayFlow CytometryHumansKidney TransplantationLymphocyte ActivationLymphocyte CountMiddle AgedPostoperative ComplicationsT-LymphocytesComparative StudyJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Martina Sester, Urban Sester, Susana Alarcon Salvador, Gunnar Heine, Sabine Lipfert, Matthias Girndt, Barbara Gärtner, Hans Köhler. 2002-04-30. Age-related decrease in adenovirus-specific T cell responses.. https://doi.org/10.1086/340502

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2005

SUMO modification of the Ets-related transcription factor ERM inhibits its transcriptional activity.

A variety of transcription factors are post-translationally modified by SUMO, a 97-residue ubiquitin-like protein bound covalently to the targeted lysine. Here we describe SUMO modification of the Ets family member ERM at positions 89, 263, 293, and 350. To investigate how SUMO modification affects the function of ERM, Ets-responsive intercellular adhesion molecule 1 (ICAM-1) and E74 reporter plasmids were employed to demonstrate that SUMO modification causes inhibition of ERM-dependent transcription without affecting the subcellular localization, stability, or DNA-binding capacity of the protein. When the adenoviral protein Gam1 or the SUMO protease SENP1 was used to inhibit the SUMO modification pathway, ERM-dependent transcription was de-repressed. These results demonstrate that ERM is subject to SUMO modification and that this post-translational modification causes inhibition of transcription-enhancing activity.

Adenoviridae↗
PubMed2002

Endothelial cell-derived lipase mediates uptake and binding of high-density lipoprotein (HDL) particles and the selective uptake of HDL-associated cholesterol esters independent of its enzymic activity.

Endothelial cell-derived lipase (EDL) is a new member of the lipase gene family with high sequence homology with lipoprotein lipase (LPL). EDL is a phospholipase with very little triacylglycerol lipase activity. To investigate the effects of EDL on binding and uptake of high-density lipoprotein (HDL), as well as on the selective uptake of HDL-derived cholesterol esters (CEs), HepG2 cells were infected with adenovirus coding for EDL. For comparison, cells were also infected with LPL and with lacZ as a control. Both HDL binding and particle uptake were increased 1.5-fold and selective HDL-CE uptake was increased 1.8-fold in EDL-infected HepG2 cells compared with controls. The effect of LPL was less pronounced, resulting in 1.1-fold increase in particle uptake and 1.3-fold increase in selective uptake. Inhibition of the enzymic activity with tetrahydrolipstatin (THL) significantly enhanced the effect of EDL, as reflected by a 5.2-fold increase in binding, a 2.6-fold increase in particle uptake and a 1.1-fold increase in CE selective uptake compared with incubations without THL. To elucidate the mechanism responsible for the effects of THL, we analysed the abundance of heparin-releasable EDL protein from infected HepG2 cells upon incubations with THL, HDL and free (non-esterified) fatty acids (FFAs). In the presence of THL, vastly more EDL protein remained bound to the cell surface. Additionally, HDL and FFAs reduced the amount of cell-surface-bound EDL, suggesting that fatty acids that are liberated from phospholipids in HDL release EDL from the cell surface. This was substantiated further by the finding that, in contrast with EDL, the amount of cell-surface-bound enzymically inactive mutant EDL (MUT-EDL) was not reduced in the presence of HDL and foetal calf serum. The increased amount of cell-surface-bound MUT-EDL in the presence of THL suggested that the enzymic inactivity of MUT-EDL, as well as an augmenting effect of THL that is independent of its ability to inactivate the enzyme, are responsible for the increased amount of cell-surface-bound EDL in the presence of THL. Furthermore, in cells expressing MUT-EDL, binding and holoparticle uptake were markedly higher compared with cells expressing the active EDL, and could be increased further in the presence of THL. Despite 1.7-fold higher binding and 1.8-fold higher holoparticle uptake, the selective CE uptake by MUT-EDL-expressing cells was comparable with EDL-expressing cells and was even decreased 1.3-fold with THL. Experiments in CLA-1 (CD-36 and LIMPII analogous 1, the human homologue of scavenger receptor class B type I)-deficient HEK-293 cells demonstrated that EDL alone has the ability to stimulate HDL-CE selective uptake independently of CLA-1. Thus our results demonstrate that EDL mediates both HDL binding and uptake, and the selective uptake of HDL-CE, independently of lipolysis and CLA-1.

Adenoviridae↗
PubMed2002

Transcriptional regulation of the human glycoprotein hormone common alpha subunit gene by cAMP-response-element-binding protein (CREB)-binding protein (CBP)/p300 and p53.

We have investigated the functional interactions between adenovirus early region 1A (AdE1A) protein, the co-activators cAMP-response-element-binding protein (CREB)-binding protein (CBP)/p300 and SUG1, and the transcriptional repressor retinoblastoma (Rb) in mediating T3-dependent repression. Utilizing the human glycoprotein hormone common alpha-subunit (alpha-subunit) promoter and AdE1A mutants with selective binding capacity to these molecules we have determined an essential role for CBP/p300. In normal circumstances, wild-type 12 S AdE1A inhibited alpha-subunit activity. In contrast, adenovirus mutants that retain both the SUG1- and Rb-binding sites, but lack the CBP/p300-binding site, were unable to repress promoter activity. We have also identified a role for the tumour-suppressor gene product p53 in regulation of the alpha-subunit promoter. Akin to 12 S AdE1A, exogenous p53 expression repressed alpha-subunit activity. This function resided in the ability of p53 to interact with CBP/p300; an N-terminal mutant incapable of interacting with CBP/p300 did not inhibit alpha-subunit activity. Stabilization of endogenous p53 by UV irradiation also correlated positively with reduced alpha-subunit activity. Intriguingly, T3 stimulated endogenous p53 transcriptional activity, implicating p53 in T3-dependent signalling pathways. These data indicate that CBP/p300 and p53 are key regulators of alpha-subunit activity.

Adenoviridae↗