CD28-mediated activation in CD45RA+ and CD45RO+ T cells: enhanced levels of reactive oxygen intermediates and c-Rel nuclear translocation in CD45RA+ cells

Lahdenpohja, Nina; Hurme, Mikko

doi:10.1002/jlb.63.6.775

Cited by 14 publications

(8 citation statements)

References 25 publications

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“…As a disparity of NF‐κB activation between CD45RO + and CD45RA + T cells has been uncovered in normals (11, 16), we sought to determine whether this relationship would work in asthmatics. Interestingly, we observed that NF‐κB was more strongly activated in CD45RO + T cells than in CD45RA + T cells, possibly harmonizing the fact that there are higher numbers of inflammatory cytokine‐producing cells within this subset from asthmatics (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…These mutations prevent IκBαM phosphorylation, trapping NF‐κB in its inactivated cytoplasmic location complexed with IκBαM. NF‐κB repression has been linked with T‐cell tolerance and decreased capacity to produce TCR and effector cytokines, such as interferon (IFN)‐γ, IL‐2, and IL‐4 (11). Targeted NF‐κB inhibition by AdIκBαM induced apoptosis and downregulated B7 molecules in DCs, highlighting an important mechanism for T‐cell tolerance (12).…”

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confidence: 99%

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Selective blockade of NF‐κB by novel mutated IκBα suppresses CD3/CD28‐induced activation of memory CD4⁺ T cells in asthma

Zhou

Zhang

et al. 2007

Allergy

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Selective blockade of NF‐κB by novel mutated IκBα suppresses CD3/CD28‐induced activation of memory CD4⁺ T cells in asthma

Zhou

Zhang

et al. 2007

Allergy

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“…Several studies have shown that intracellular oxidative stress, as a result of activation, also initiates apoptotic processes in primary T cells. [22][23][24]53 More recently, it has been proposed that selective oxidation of phosphatidylserine during oxidative stress promotes its externalization. 54 By using dichlorofluorescein, an indicator of generalized oxidative stress, we have shown that human peripheral blood T cells activated in vitro produced intracellular ROS.…”

Section: Discussionmentioning

confidence: 99%

Red blood cells inhibit activation-induced cell death and oxidative stress in human peripheral blood T lymphocytes

Fonseca

Porto

Uchida

et al. 2001

Blood

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IntroductionProgrammed cell death, or apoptosis, is a physiological process that contributes to the homeostasis of multicellular organisms. Apoptosis resulting from activation of T cells-ie, activationinduced cell death (AICD)-is thought to serve as a feedback mechanism that deletes activated T cells. 1 Contrary to immature thymocytes and transformed T-cell lines, resting T cells are highly resistant to apoptosis after initial activation but then become highly susceptible. [2][3][4] Accordingly, most studies on AICD have focused on the study of interactions between the death receptors, CD95 (Fas) and tumor necrosis factor (TNF)-␣ receptor, with their agonists, CD95L (Fas ligand) and TNF-␣, on activated T cells and T-cell hybridomas 5,6 (for review, see 7 ). Quiescent normal T cells express low or nondetectable levels of CD95 and CD95L, but mitogenic activation of primary T cells markedly increases their expression. 8,9 Other members of the TNF-␣ receptor family, such as TRAIL-R1 and TRAIL-R2, can also trigger apoptosis in susceptible cells after binding of their ligands. 7 Despite the important role played by the death receptors, growing evidence indicates that environmental constituents, such as nonlymphoid secreted factors and cytokines, can modulate apoptosis of activated T cells, thus emphasizing the significance of the environment in the maintenance of T-cell homeostasis. [10][11][12] Any imbalance in the apoptotic process may result in either of 2 possible scenarios: lymphocyte accumulation or lymphocyte depletion. In the former, lymphoproliferative disorders-now designated as autoimmune lymphoproliferative syndrome-result from downregulated in vivo apoptosis, develop in mice and in humans, result from genetic mutations in CD95 or its ligand, and are associated with autoimmune phenomena. [13][14][15][16] In the latter scenario, lymphopenia resulting from up-regulated in vivo apoptosis is the clinical finding in human immunodeficiencies, such as idiopathic CD4 ϩ T lymphocytopenia, and it correlates with increased levels of CD95 and CD95L, a finding also observed in patients with CD8 ϩ T lymphopenia. 17 Lymphocytopenias found in adults could also result from adenosine deaminase deficiency. 18 Other factors implicated in different forms of apoptosis are reactive oxygen species (ROS). Several studies have provided evidence for the involvement of ROS in apoptosis of T-cell blasts and hybridomas by using antioxidants such as N-acetyl cysteine and glutathione. 19,20 Apoptosis in these cells is the consequence of changes in mitochondrial permeability and the subsequent release of ROS. 21 Studies performed with primary T cells, however, indicate that the formation of intracellular ROS is necessary for T-cell activation and IL-2 secretion but also regulates activationinduced T-cell apoptosis, therefore suggesting that intracellular ROS could play a role in peripheral T-cell homeostasis. [22][23][24] Nevertheless, studies with primary T cells are usually performed in cultures lacking other "nonlymphoid" cells, albeit...

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“… 41,42 Recent studies in our laboratory support the notion that the functions of neonatal T cells differ from those of adult naive T cells; after anti‐CD3+anti‐CD28 stimulation CD45RA + and CD45RO + T cells of adults produced equally high IL‐2 levels, and induction of NF‐κB activation and ROI formation were stronger in naive than in memory T cells of adults. 43 …”

Section: Discussionmentioning

confidence: 99%

Low CD3+CD28‐induced interleukin‐2 production correlates with decreased reactive oxygen intermediate formation in neonatal T cells

Kilpinen

Hurme

1998

Immunology

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SUMMARYThe capacity of neonatal T cells to secrete interleukin-2 (IL-2) has been reported to be variable. We analysed IL-2 production in purified neonatal and adult T cells using polyclonal activator phorbol ester+calcium ionophore (PDBu+iono) or receptor-mediated anti-CD3/anti-CD3+anti-CD28 stimulation. PDBu+iono induced equally high IL-2 levels in both groups and, when stimulated with plate-bound anti-CD3 monoclonal antibody (mAb), the IL-2 secretion by neonatal cells was undetectable and adult cells produced low amounts of IL-2 (mean 331±86 pg/ml ). The addition of anti-CD28 mAb to anti-CD3-stimulated cells markedly increased IL-2 production in both cell types, but levels of IL-2 in neonatal T cells remained clearly lower than those of adult T cells (respective mean values: 385±109 pg/ml and 4494±1199 pg/ml ). As NF-kB is a critical transcription factor in the control of IL-2 expression, we next analysed its nuclear translocation in neonatal and adult T cells using the electrophoretic mobility shift assay and, because induction of reactive oxygen intermediates (ROI ) is required for the activation of NF-kB, we also analysed levels of intracellular ROI in these cells using the ROI-reactive fluorochrome DCFH-DA and flow cytometry. In neonatal T cells NF-kB activation and ROI formation after anti-CD3 stimulation were low compared with adult T cells and, although addition of anti-CD28 mAb increased induction of NF-kB and ROI formation, levels similar to those of adults were not achieved. After PDBu+iono stimulation, the cells showed similar ROI formation and IL-2 secretion. Our results suggest that reduced IL-2 production by neonatal T cells is specific for anti-CD3 and anti-CD3+anti-CD28-mediated stimulation and that these activators cannot effectively activate the ROI-NF-kB signalling pathway in neonatal T cells.

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CD28-mediated activation in CD45RA+ and CD45RO+ T cells: enhanced levels of reactive oxygen intermediates and c-Rel nuclear translocation in CD45RA+ cells

Cited by 14 publications

References 25 publications

Selective blockade of NF‐κB by novel mutated IκBα suppresses CD3/CD28‐induced activation of memory CD4⁺ T cells in asthma

Selective blockade of NF‐κB by novel mutated IκBα suppresses CD3/CD28‐induced activation of memory CD4⁺ T cells in asthma

Red blood cells inhibit activation-induced cell death and oxidative stress in human peripheral blood T lymphocytes

Low CD3+CD28‐induced interleukin‐2 production correlates with decreased reactive oxygen intermediate formation in neonatal T cells

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CD28-mediated activation in CD45RA+ and CD45RO+ T cells: enhanced levels of reactive oxygen intermediates and c-Rel nuclear translocation in CD45RA+ cells

Cited by 14 publications

References 25 publications

Selective blockade of NF‐κB by novel mutated IκBα suppresses CD3/CD28‐induced activation of memory CD4+ T cells in asthma

Selective blockade of NF‐κB by novel mutated IκBα suppresses CD3/CD28‐induced activation of memory CD4+ T cells in asthma

Red blood cells inhibit activation-induced cell death and oxidative stress in human peripheral blood T lymphocytes

Low CD3+CD28‐induced interleukin‐2 production correlates with decreased reactive oxygen intermediate formation in neonatal T cells

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Selective blockade of NF‐κB by novel mutated IκBα suppresses CD3/CD28‐induced activation of memory CD4⁺ T cells in asthma

Selective blockade of NF‐κB by novel mutated IκBα suppresses CD3/CD28‐induced activation of memory CD4⁺ T cells in asthma