title: Altered CD46-mediated T cell co-stimulation in haemodialysis patients.
abstract: 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.
authors.affiliation: V. Medical Department (Nephrology), University Hospital Mannheim, University of Heidelberg, Germany. paul.brinkkoetter@med5.ma.uni-heidelberg.de
authors.forename: P-T
authors.initials: PT
authors.lastname: Brinkkoetter
authors.forename: S
authors.initials: S
authors.lastname: Marinaki
authors.forename: U
authors.initials: U
authors.lastname: Gottmann
authors.forename: S
authors.initials: S
authors.lastname: Fleckenstein
authors.forename: C
authors.initials: C
authors.lastname: Stump
authors.forename: F J
authors.initials: FJ
authors.lastname: Van Der Woude
authors.forename: C
authors.initials: C
authors.lastname: Braun
authors.forename: B A
authors.initials: BA
authors.lastname: Yard
mesh_terms: 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
chemical_list: D015703:Antigens, CD; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D016753:Interleukin-10
references.citation: J Immunol. 2000 Feb 15;164(4):1839-46
references.pmid: 10657632
references.citation: Nephrol Dial Transplant. 1999 Oct;14(10):2343-50
references.pmid: 10528656
references.citation: Kidney Int. 2000 Oct;58(4):1758-64
references.pmid: 11012910
references.citation: Mol Cell Biochem. 2000 Sep;212(1-2):45-50
references.pmid: 11108135
references.citation: Kidney Int. 2001 Feb;59(2):407-14
references.pmid: 11168922
references.citation: Kidney Int. 2001 Mar;59(3):883-92
references.pmid: 11231343
references.citation: Kidney Int. 2001 Apr;59(4):1382-9
references.pmid: 11260399
references.citation: Am J Kidney Dis. 2001 Aug;38(2):286-95
references.pmid: 11479154
references.citation: J Immunol. 2001 Dec 15;167(12):6780-5
references.pmid: 11739493
references.citation: Kidney Int. 2001 Dec;60(6):2385-91
references.pmid: 11737614
references.citation: Nat Immunol. 2002 Jul;3(7):659-66
references.pmid: 12055630
references.citation: Kidney Int. 2002 Sep;62(3):949-55
references.pmid: 12164877
references.citation: Nature. 2003 Jan 23;421(6921):388-92
references.pmid: 12540904
references.citation: Scand J Urol Nephrol. 2003;37(1):71-6
references.pmid: 12745749
references.citation: Pharmacol Rev. 2003 Jun;55(2):241-69
references.pmid: 12773629
references.citation: Nephrol Dial Transplant. 2003 Jul;18 Suppl 5:v41-4
references.pmid: 12817068
references.citation: Nephrol Dial Transplant. 2003 Oct;18(10):1976-9
references.pmid: 13679468
references.citation: Nat Med. 2003 Oct;9(10):1287-92
references.pmid: 14502281
references.citation: JAMA. 1980 Nov 21;244(20):2310-1
references.pmid: 7431555
references.citation: Ann Intern Med. 1980 Oct;93(4):597-613
references.pmid: 7001976
references.citation: Kidney Int. 1984 Jan;25(1):124-8
references.pmid: 6233450
references.citation: J Immunol. 1987 Jun 1;138(11):3850-5
references.pmid: 3584971
references.citation: J Clin Invest. 1987 Sep;80(3):743-9
references.pmid: 3497950
references.citation: Kidney Int. 1989 Oct;36(4):636-44
references.pmid: 2681933
references.citation: Kidney Int. 1990 Dec;38(6):1164-8
references.pmid: 2150086
references.citation: Nephron. 1991;58(3):268-75
references.pmid: 1896091
references.citation: Nephron. 1991;59(1):41-5
references.pmid: 1944746
references.citation: Dtsch Med Wochenschr. 1993 May 28;118(21):790-5
references.pmid: 8504715
references.citation: J Immunol. 1993 Aug 1;151(3):1519-27
references.pmid: 8335944
references.citation: Kidney Int. 1993 Aug;44(2):359-65
references.pmid: 7690861
references.citation: Blood Purif. 1994;12(1):36-41
references.pmid: 7986474
references.citation: J Am Soc Nephrol. 1998 Sep;9(9):1689-96
references.pmid: 9727378
references.citation: Kidney Int. 1999 Mar;55(3):1081-90
references.pmid: 10027947
references.citation: J Immunol. 2000 Jun 15;164(12):6091-5
references.pmid: 10843656