IFN-<i>β</i>1a Modulates the Expression of CTLA-4 and CD28 Splice Variants in Human Mononuclear Cells: Induction of Soluble Isoforms

Giorelli, Maurizio; Livrea, Paolo; Defazio, Giovanni; Ricchiuti, Felicia; Pagano, Eleonora Samanta; Trojano, María

doi:10.1089/107999001753238042

Cited by 21 publications

(13 citation statements)

References 24 publications

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“…These altered cytokine profiles may dysregulate T cell activation and function, leading to the elevation of soluble costimulatory molecules including sCTLA-4 and sCD28. This hypothesis can also be supported by the findings of Giorelli et al [46],who demonstrated that IFN-β1a could induce sCTLA-4 and sCD28 mRNA in purified human mononuclear cells.. Despite the production by alternative mRNA splicing with deletion of transmembrane domain, we cannot exclude the possibility that these soluble molecules may also be presented by shedding of their membrane bound forms from activated T lymphocytes or APC [22].…”

Section: Discussionsupporting

confidence: 66%

Elevation of Plasma Soluble T Cell Costimulatory Molecules CTLA-4, CD28 and CD80 in Children with Allergic Asthma

Ip¹,

Wong²,

Leung

et al. 2005

Int Arch Allergy Immunol

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Background: The surface expression of T cell costimulatory molecules CTLA-4 and CD28 and their counter-ligands, B7 molecules (CD80, CD86), is differentially induced for T cell activation and expansion in allergic asthma. However, the role of their soluble forms in plasma has not yet been elucidated. In this study, we investigated whether expression is altered and whether soluble costimulatory molecules are clinically relevant in asthmatic patients. Methods: Plasma concentrations of soluble CTLA-4 (sCTLA-4), CD28, CD80 and CD86 in 51 children with chronic allergic asthma with or without inhaled corticosteroid treatment, and 22 sex- and age-matched control subjects were measured by enzyme-linked immunosorbent assay. Plasma total IgE concentration was measured using a microparticle immunoassay. Results: Asthmatic patients had higher logarithmic plasma total IgE concentration (IgE_log) than healthy subjects (p < 0.0001). In non-steroid-treated patients, plasma sCTLA-4, sCD28 and sCD80 but not sCD86 concentrations were significantly higher than those of control subjects (all p < 0.05). Plasma sCD80 and sCD86 but not sCTLA-4 and sCD28 concentrations correlated significantly with IgE_log of all subjects (p < 0.05). There were also significant positive correlations between sCTLA-4 and sCD28 (p = 0.0007), and between sCD80 and sCD86 in all asthmatic patients (p = 0.001). Conclusions: Plasma sCTLA-4, sCD28 and sCD80 concentrations are elevated in allergic asthma. The increased expression of these soluble proteins may reflect the dysregulation of T cell activation, contributing to the immunopathogenesis of allergic asthma.

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Section: Discussionsupporting

confidence: 66%

Elevation of Plasma Soluble T Cell Costimulatory Molecules CTLA-4, CD28 and CD80 in Children with Allergic Asthma

Ip¹,

Wong²,

Leung

et al. 2005

Int Arch Allergy Immunol

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“…In support of this hypothesis, administration of a soluble CTLA-4 Ig to CTLA-4 Ϫ/Ϫ mice from birth or breeding to a transgenic strain expressing high serum levels of CTLA-4 Ig was shown to delay or prevent the onset of lymphoproliferative disease (40,80). Interestingly, soluble CTLA-4, apparently produced by monocytes rather than T cells, is upregulated by IFN-␤ (27,88). Thus, viral infections, via early induction of type I interferons (8), may directly promote the secretion of biologically active CTLA-4 and regulate the extent of costimulatory activity mediated by CD80-CD86 interactions.…”

Section: Discussionmentioning

confidence: 98%

Lack of Intrinsic CTLA-4 Expression Has Minimal Effect on Regulation of Antiviral T-Cell Immunity

Homann¹,

Dummer

Wolfe

et al. 2006

J Virol

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“…In addition, such a relationship seems in some points contradictory. Indeed, it is difficult to explain why autoimmune disease susceptibility genotypes (+49G/G and CT60G/G) are associated with lower levels of sCTLA-4 transcripts [10,11,35,61,62,[69][70][71][72][73][74]. It may be hypothesized that abnormal translation of both CTLA-4 transcripts (sCTLA-4 and full-length CTLA-4) and/or abnormal intracellular trafficking and release of sCTLA-4 may occur in patients with autoimmune diseases with high levels of sCTLA-4.…”

Section: What Does Raised Sctla4 Really Mean?mentioning

confidence: 99%

The soluble CTLA-4 receptor and its role in autoimmune diseases: an update

Saverino

Simone

Bagnasco

et al. 2010

Autoimmun Highlights

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CTLA-4, initially described as a membranebound molecule, is a costimulatory receptor transducing a potent inhibitory signal. Increasing evidence shows the CTLA-4 gene to be an important susceptibility locus for autoimmune endocrinopathies and other autoimmune disorders. A soluble form of cytotoxic T-lymphocyte-associated antigen-4 (sCTLA-4) has been established and shown to possess CD80/CD86 binding activity and in vitro immunoregulatory functions. sCTLA-4 is generated by alternatively spliced mRNA. Whereas low levels of sCTLA-4 are detected in normal human serum, increased serum levels are observed in several autoimmune diseases (e.g. Graves’ disease, myasthenia gravis, systemic lupus erythematosus, type 1 diabetes, systemic sclerosis, coeliac disease, autoimmune pancreatitis and primary biliary cirrhosis). The biological significance of increased sCTLA-4 serum levels is not fully clarified yet. On the one hand, it can be envisaged that sCTLA-4 specifically inhibits early T-cell activation by blocking the interaction of CD80/CD86 with the costimulatory receptor CD28. On the other hand, higher levels of sCTLA-4 could compete for the binding of the membrane form of CTLA-4 with CD80/CD86 in the later phases of T-lymphocyte activation, causing a reduction in inhibitory signalling. This double-edged nature of sCTLA-4 to block the binding of CD28 to CD80/CD86 may result in different outcomes during the clinical course of an autoimmune disease.

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IFN-β1a Modulates the Expression of CTLA-4 and CD28 Splice Variants in Human Mononuclear Cells: Induction of Soluble Isoforms

Cited by 21 publications

References 24 publications

Elevation of Plasma Soluble T Cell Costimulatory Molecules CTLA-4, CD28 and CD80 in Children with Allergic Asthma

Elevation of Plasma Soluble T Cell Costimulatory Molecules CTLA-4, CD28 and CD80 in Children with Allergic Asthma

Lack of Intrinsic CTLA-4 Expression Has Minimal Effect on Regulation of Antiviral T-Cell Immunity

The soluble CTLA-4 receptor and its role in autoimmune diseases: an update

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