EVIDENCE OF IMPAIRED T-CELL FUNCTION IN HEMODIALYSIS-PATIENTS - POTENTIAL ROLE FOR SECONDARY HYPERPARATHYROIDISM

Previous studies in our laboratory showed that the T cell is a target for parathyroid hormone (PTH) action. It is theoretically possible, therefore, that chronic exposure of the T cells to high blood levels of PTH in patients with chronic renal failure may adversely affect T cell function. We examined in both normal subjects and dialysis patients several aspects of T cell function, including (1) T cell proliferation in response to phytohemagglutinin (PHA) mitogen with and without PTH and with and without exogenous interleukin 2 (IL-2); (2) the IL-2 production induced by PHA with and without PTH, and (3) resting levels of cytosolic calcium - [Ca2+]i - and the increment in [Ca2+]i in response to anti-CD3 antibody. Although PHA significantly (p < 0.01) stimulated proliferation of T cells from both normal subjects and dialysis patients, the magnitude of the stimulation was significantly (p < 0.01) smaller in the latter group. In both normal subjects and dialysis patients, exogenous IL-2 alone stimulated T cell proliferation, and the magnitude of the stimulation was similar to that produced by PHA. Also, IL-2 augmented PHA-induced proliferation of T cells from normal subjects, but failed to do so in T cells from dialysis patients. PHA did not augment IL-2 production by T cells from dialysis patients, and PTH did not correct this defect. The resting levels of [Ca2+]i in T cells from dialysis patients were significantly (p < 0.01) higher, and the increments in [Ca2+]i in response to anti-CD3 antibody were significantly (p < 0.01) lower than in T cells from normal subjects. The data demonstrate that the T cell function is impaired in dialysis patients. It is proposed that chronic exposure to high blood levels of PTH in the dialysis patients is associated with a rise in resting levels of [Ca2+]i and with a reduced calcium signal in response to anti-CD3 antibody, and these cellular derangements may interfere with the proper response of T cells to mitogens.