The imbalance in the ratio of Th1 and Th2 helper lymphocytes in uraemia is mediated by an increased apoptosis of Th1 subset.
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-gamma (IFN-gamma) 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-gamma (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.
Alvarez-Lara
Maria Antonia
MA
Nephrology Service, Reina Sofía University Hospital, 14004 Córdoba, Spain. malvarezlaras@senefro.org
Carracedo
Julia
J
Ramírez
Rafael
R
Martín-Malo
Alejandro
A
Rodríguez
Mariano
M
Madueño
Juan Antonio
JA
Aljama
Pedro
P
D000328:Adult; D000368:Aged; D017209:Apoptosis; D002908:Chronic Disease; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D014511:Uremia / Q000276:immunology* / Q000473:pathology
D003404:Creatinine