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 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.
Brinkkoetter
P-T
PT
V. Medical Department (Nephrology), University Hospital Mannheim, University of Heidelberg, Germany. paul.brinkkoetter@med5.ma.uni-heidelberg.de
Marinaki
S
S
Gottmann
U
U
Fleckenstein
S
S
Stump
C
C
Van Der Woude
F J
FJ
Braun
C
C
Yard
B A
BA
D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D000704:Analysis of Variance; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D003167:Complement Activation; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000628:therapy*; D008213:Lymphocyte Activation; D008297:Male; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D010530:Peritoneal Dialysis; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D006435:Renal Dialysis; D018709:Statistics, Nonparametric
D015703:Antigens, CD; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D016753:Interleukin-10
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