Impaired T cell proliferation, increased soluble death-inducing receptors and activation-induced T cell death in patients undergoing haemodialysis.
Haemodialysis is a widespread option for end-stage renal disease (ESRD). Long-term success of dialysis is, however, limited by a high rate of serious bacterial and viral infections. We compared T cell functions in ESRD patients undergoing haemodialysis (n = 20), or were not dialysed and received conventional medical treatment (n = 20). Healthy volunteers (n = 15) served as controls. The T cell phenotype was examined by immunofluorescence using fluorochrome-labelled monoclonal antibodies and FACS analysis. The concentration of soluble CD95/Fas and of tumour necrosis factor-alpha receptor type 1 (sTNFR1) in the sera was quantified by ELISA. Activation-induced programmed T cell death was triggered by anti-CD3/CD28 antibodies and measured by 7-AAD staining. All immunological tests were performed at least 1 month after dialysis initiation. T cell proliferation in response to phytohaemagglutinin or anti-CD3 monoclonal antibodies was moderately diminished in non-dialysed patients and markedly reduced in haemodialysis patients compared to healthy controls (P < 0.01 and P < 0.001, respectively). In a mixed lymphocyte culture the proliferative response of T cells from dialysed patients was significantly diminished (P < 0.001). T cells of both non-dialysed and dialysed patients have augmented CD95/Fas and CD45RO expression, increased sCD95/Fas and sTNFR1 release and spontaneously undergo apoptosis. Culture of T cells from haemodialysis patients with anti-CD3/CD28 antibodies increased the proportion of CD4(+) T cells committing activation-induced cell death by a mean 7.5-fold compared to T-helper cells from non-dialysed patients (P < 0.001). Renal failure and initiation of haemodialysis results in a reduced proliferative T cell response, an aberrant state of T cell activation and heightened susceptibility of CD4(+) T cells to activation-induced cell death.
Ankersmit
H J
HJ
Department of Surgery, General Hospital of Vienna University, Vienna, Austria. hjankersmit@hotmail.com
Deicher
R
R
Moser
B
B
Teufel
I
I
Roth
G
G
Gerlitz
S
S
Itescu
S
S
Wolner
E
E
Boltz-Nitulescu
G
G
Kovarik
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis*; D017209:Apoptosis; D002455:Cell Division; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology* / Q000628:therapy; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D047888:Receptors, Tumor Necrosis Factor, Type I; D006435:Renal Dialysis; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019014:fas Receptor / Q000096:biosynthesis*
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D019014:fas Receptor; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1