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Altered CD46-mediated T cell co-stimulation in haemodialysis patients

While most of our understanding of immune dysfunction in dialysis patients involves alterations in CD28-CD80/86 signalling, nothing is known of CD46-mediated co-stimulation of T cells in these patients. Because C3b/C4b bind to CD46 and complement activation occurs during haemodialysis (HD), we addre...

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Main Authors: Brinkkötter, Paul-Thomas (Author) , Marinaki, Smaragdi (Author) , Göttmann, Uwe (Author) , Fleckenstein, Sandra Magdalena (Author) , Stump-Guthier, Carolin (Author) , Woude, Fokko J. van der (Author) , Braun, Claude (Author) , Yard, Benito A. (Author)
Format: Article (Journal)
Language:English
Published: 2005
In: Clinical & experimental immunology
Year: 2005, Volume: 139, Issue: 3, Pages: 534-541
ISSN:1365-2249
DOI:10.1111/j.1365-2249.2005.02705.x
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/j.1365-2249.2005.02705.x
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Author Notes:P.-T. Brinkkoetter, S. Marinaki, U. Gottmann, S. Fleckenstein, C. Stump, F.J. Van Der Woude, C. Braun and B.A. Yard

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245 1 0 |a Altered CD46-mediated T cell co-stimulation in haemodialysis patients  |c P.-T. Brinkkoetter, S. Marinaki, U. Gottmann, S. Fleckenstein, C. Stump, F.J. Van Der Woude, C. Braun and B.A. Yard 
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520 |a While most of our understanding of immune dysfunction in dialysis patients involves alterations in CD28-CD80/86 signalling, nothing is known of CD46-mediated co-stimulation of T cells in these patients. Because C3b/C4b bind to CD46 and complement activation occurs during haemodialysis (HD), we addressed whether CD46-mediated T cell activation is altered in HD (n = 9), peritoneal dialysis (PD) (n = 10) and predialysis patients (n = 8) compared to healthy controls (HC) (n = 8). T cell surface markers, T cell proliferation and interleukin (IL)-10 production were studied in CD4(+)T cells. In addition, CD46 splice-variants and IL-10 promoter gene polymorphisms were studied by reverse transcription (RT) or amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), respectively. In all uraemic patients, irrespective of the stage of renal insufficiency or dialysis modality, a significant increase in the percentage of CD25 positivity in naive CD4(+)T cells was found (64% +/- 21%versus 23% +/- 18%, P < 0.001). Lymphocytes of HD patients proliferated in greater numbers and produced more IL-10 after co-stimulation with anti-CD46 than after co-stimulation with anti-CD28. This was also found in CD4(+)T cells of PD patients, albeit to a lesser extent. In contrast, with T cells of predialysis patients and of HC, co-stimulation via CD28 was more efficient. The observed alterations in T cell proliferation and IL-10 production were associated neither with CD46 splice variants nor with IL-10 promoter gene polymorphisms. Lymphocytes of HD patients show an increased response on CD46 co-stimulation. These data suggest that ongoing complement activation in HD patients may lead to alterations in acquired immunity. 
650 4 |a Aged 
650 4 |a Aged, 80 and over 
650 4 |a Alternative Splicing 
650 4 |a Analysis of Variance 
650 4 |a Antigens, CD 
650 4 |a Case-Control Studies 
650 4 |a CD4-Positive T-Lymphocytes 
650 4 |a Cell Proliferation 
650 4 |a Complement Activation 
650 4 |a Female 
650 4 |a Humans 
650 4 |a Interleukin-10 
650 4 |a Kidney Failure, Chronic 
650 4 |a Lymphocyte Activation 
650 4 |a Male 
650 4 |a Membrane Cofactor Protein 
650 4 |a Membrane Glycoproteins 
650 4 |a Middle Aged 
650 4 |a Peritoneal Dialysis 
650 4 |a Polymorphism, Genetic 
650 4 |a Promoter Regions, Genetic 
650 4 |a Renal Dialysis 
650 4 |a Statistics, Nonparametric 
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