Journal Article

The imbalance in the ratio of Th1 and Th2 helper lymphocytes in uraemia is mediated by an increased apoptosis of Th1 subset

Maria Antonia Alvarez-Lara, Julia Carracedo, Rafael Ramírez, Alejandro Martín-Malo, Mariano Rodríguez, Juan Antonio Madueño and Pedro Aljama

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 19, issue 12, pages 3084-3090
Published in print December 2004 | ISSN: 0931-0509
Published online December 2004 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfh382
The imbalance in the ratio of Th1 and Th2 helper lymphocytes in uraemia is mediated by an increased apoptosis of Th1 subset

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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-γ (IFN-γ) 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-γ (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

Journal Article.  4620 words.  Illustrated.

Subjects: Nephrology

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