Nephrol Dial Transplant Vol. 19 No. 12 © ERA-EDTA 2004; all rights reserved
Original Article
The imbalance in the ratio of Th1 and Th2 helper lymphocytes in uraemia is mediated by an increased apoptosis of Th1 subset
1 Nephrology Service and 2 Research Unit, Reina Sofía University Hospital, Córdoba, Spain
Correspondence and offprint requests to: Ma Antonia Alvarez-Lara, Servicio de Nefrologia, Hospital Reina Sofia, Av. Menendez Pidal s/n, 14004 Cordoba, Spain. Email: malvarezlaras{at}senefro.org
Background. In uraemia there is a reduction in the total number of T lymphocytes and an imbalance in the ratio of Th1/Th2 T-helper (Th) lymphocytes. A higher rate of apoptosis in T lymphocytes has been reported in haemodialysis patients. The aims of the present study were to assess the Th1/Th2 pattern in uraemia and to evaluate whether a relative increase in Th1 apoptosis may explain the Th1/Th2 imbalance observed in uraemic patients.
Methods. Seventeen non-dialysed uraemic patients were evaluated; eight healthy volunteers served as controls. Intracellular interferon-
(IFN-) and interleukin-4 (IL-4) were measured by direct intracellular immunofluorescence and flow cytometry. Apoptosis was determined by flow cytometry using annexin V or TUNEL. Mechanisms of apoptosis were assessed by determination of Fas and Bcl-2 expression.
Results. Cell production of cytokines is significantly higher in uraemic patients than in controls. In addition, in uraemic patients only 5.1±2.1% of the T lymphocytes contained IFN- (Th1 cells) while 61.9± 14.8% contained IL-4 (Th2 cells) (P<0.0001). The percentage of apoptosis was 29.6±6.3% and 4.7± 1.6% in Th1 and Th2 lymphocytes, respectively (P<0.001). Fas expression was higher in Th1 than in Th2 cells and the expression of Bcl-2 was lower in Th1 than in Th2 cells. The apoptosis induced by anti-Fas antibodies was similar in both types of lymphocytes.
Conclusions. In uraemia there is a reduction in the proportion of Th1 lymphocytes due to a higher rate of apoptosis in this subset of lymphocytes. Th1 from uraemic patients show a higher expression of Fas and a lower expression of Bcl-2 than Th2. This makes uraemic Th1 cells more susceptible to apoptosis. The Th1/Th2 imbalance may contribute to alterations in cellular immunity observed in chronic kidney disease patients.
Keywords: apoptosis; Bcl-2; chronic kidney disease; cytokines; Fas; Th1/Th2 lymphocytes
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