Inadequate ability of T-lymphocytes from chronic uremic subjects to stimulate the in vitro growth of committed erythroid progenitors (BFU-E).
The growth of normal burst-forming units (BFU-E) is known to depend on a burst-promoting activity (BPA) produced by T-lymphocytes. Few BFU-E colonies have been observed in cultures of blood mononuclear cells (MNC) of uremic patients. The aim of the present study was to examine the concentration of BFU-E in the blood of uremic patients and to evaluate the ability of uremic T-lymphocytes to produce BPA. We have studied 6 chronic uremic patients treated with maintenance hemodialysis. When 5 X 10(5) blood MNC depleted of T-lymphocytes of uremic subjects were stimulated by 1 X 10(6) normal T-lymphocytes in a methylcellulose culture system we observed the growth of a number of BFU-E colonies that did not differ significantly from normal (29 +/- 11.8 colonies). On the contrary, when 5 X 10(5) blood MNC depleted of T-lymphocytes of normal subjects were stimulated by 1 X 10(6) T-lymphocytes of uremic patients, the number of BFU-E colonies obtained was significantly lower than normal (1.9 +/- 3.1 colonies). These data show that the decreased number of BFU-E colonies obtained from blood MNC of uremic patients is due to a defect of uremic T-lymphocytes. The impairment of T-lymphocytes can be due to inhibitors of T-lymphocyte function or to variations in T cell subsets, leading to a decrease in the OKT4/OKT8 cell ratio. In any case it is a significant pathogenetic mechanism contributing to anemia in chronic uremia.
D000328:Adult; D002908:Chronic Disease; D004921:Erythropoietin / Q000494:pharmacology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000502:physiology*; D014511:Uremia / Q000276:immunology*
D004921:Erythropoietin