T lymphocyte subsets in chronic uremic patients treated with maintenance hemodialysis

Inhibition of BFU-E in vitro Growth and of Burst-Promoting Activity of T Lymphocytes by Serum of Chronic Uremic Patients Receiving Hemodialysis

“…These data are in agreement with previous results showing that T lymphocytes of uremic patients, even when removed from the uremic environment, were not able to stimu late the in vitro growth of normal BFU-E [1], It is not known why the inhibition by uremic toxins is more severe and persistent in T lymphocytes than in BFU-E. The alteration of T lymphocyte subpopula tions, with reduction of the T4 subset and of T4/T8 ratio [2], may contribute to aggravate the defect of T lymphocytes. Alternatively inhibition of BFU-E and of T lymphocytes could be due to different toxins.…”

“…An imbalance of T cell subpopulations, with reduction of T4 helper-inducer lymphocytes and lowering of the T4/T8 ratio, has also been reported in uremic patients [2]. The plasma of uremic subjects has been shown to inhibit erythroid stem cell proliferation, a number of uremic inhibitors having been implicated [3][4][5][6][7][8][9][10].…”

Inadequate Ability of T-Lymphocytes from Chronic Uremic Subjects to Stimulate the in vitro Growth of Committed Erythroid Progenitors (BFU-E)

“…Different pathogenetic mech anisms have been implicated to explain the relatively nonresponsive erythron, such as defective erythro poietin production in response to hypoxia or anemia [1] and suppression of committed erythroid precur sors (CFU-E) and of their progenies by an inhibition factor present in the uremic milieu [2][3][4][5]. We have shown that the in vitro growth of burst-forming units (BFU-E) of uremic patients is impaired and that uremic serum inhibits the growth in methylcellulose of normal BFU-E, the serum inhibition being abol ished by hemodialysis [6]. However it was not known if the decrease of colony growth was due to the im pairment of the BFU-E itself or/and to deficiency of factors stimulating their growth.…”

Effect of Cimetidine on Peripheral Blood Lymphocytes from Chronic Uremic Patients: Improvement of Burst-Promoting Activity

“…However, the BPA of uremic lymphocytes treated with cimetidine remains sig nificantly lower than that of normal lymphocytes treated with cimetidine, only approaching the BPA of normal T lymphocytes that have not been exposed to cimetidine. The slight reduction of blood OKT4+ helper subset we 111 have previously demonstrated in uremic patients [12] can account only in part for the subnormal response of uremic T lymphocytes to cimetidine. On the other hand, Cimeti dine is also shown to improve only partially the BPA of normal T lymphocytes previously incubated with uremic serum.…”

“…However, as data suggest the existence of BPA different from IL-3 [8], at the present time, BPA remains a suitable definition for factor(s) that increase the number or survival of eryth roid burst-forming units (BFU-E) [9], The BPA of T lymphocytes from uremic subjects treated with intermittent hemodialysis has been shown to be significantly impaired [10]. The sera of the same pa tients inhibited the BPA of normal T lymphocytes, hemo dialysis being rather ineffective in removing the serum inhibitor(s) [11], Both total T lymphocytes and the helperinducer subset, identified by OKT4 monoclonal antibod ies, have been found to be significantly lower than normal in uremic subjects, the cytotoxic-suppressor OKT8+ cells being only moderately reduced [12], Cimetidine is re ported both to abrogate the in vitro effects of suppressor T lymphocytes on peripheral blood lymphocyte activation [13][14][15][16][17][18][19][20] and to decrease the in vivo excessive suppressor cell activity [21,22]. Recently, we showed that cimetidine was able to improve the in vitro production of BPA by nor mal T lymphocytes, having no direct effect on the BFU-E growth [23].…”