ABSTRACT
The in vitro growth of circulating erythroid progenitors (BFU-E) populations and the production of burst-promoting activity (BPA) by T lymphocytes have been studied in 17 patients with myelodysplastic syndromes. Based on the in vitro growth patterns of BFU-E, four groups of patients have been identified: i) normal BFU-E growth; ii) low spontaneous BFU-E growth, but normal response to LCM; iii) impaired BFU-E response to LCM; iv) no BFU-E growth. The pattern of BFU-E growth seems to be related to the clinical stage of the disease rather than to the FAB subgroup to which the patients belong. The ability of T lymphocytes to stimulate BFU-E growth was significantly reduced in all patients. The possible mechanisms inducing the impaired production of BPA by T lymphocytes are discussed. The in vitro evaluation of circulating erythroid precursors can supply useful prognostic information and possibly indications concerning the responsiveness of erythropoietic stem cells to recombinant human erythropoietin in vivo.
Subject(s)
Erythroid Precursor Cells/cytology , Myelodysplastic Syndromes/immunology , T-Lymphocytes/immunology , Aged , Aged, 80 and over , Cell Division/drug effects , Colony-Forming Units Assay , Culture Media, Conditioned/pharmacology , Erythroid Precursor Cells/immunology , Female , Humans , In Vitro Techniques , Male , Middle AgedABSTRACT
The effect of aging on hematopoiesis and bone marrow exhaustion have long been debated. Unexplained anemia and impaired in vitro proliferation of erythroid precursors is frequently observed in the elderly. As hydrocortisone is known to increase the BFU-E in vitro growth, we have studied the response of BFU-E to hydrocortisone in a group of nonanemic elderly subjects. The BFU-E growth in methylcellulose from blood mononuclear cells (MNC), stimulated by lymphocyte-conditioned medium (LCM), either with or without hydrocortisone, of 10 subjects aged 76-91 years was compared with the BFU-E growth from MNC of a group of ten young subjects. While LCM induced a significant increase of BFU-E growth, both in young and old subjects, hydrocortisone induced a significant increase of BFU-E growth only in young subjects. This study shows that in the elderly, there is a latent defect of erythropoiesis, possibly consisting of a defective ability to modulate the receptors for erythropoietin on BFU-E, and that hydrocortisone offers a useful tool to identify it.
Subject(s)
Cell Division/drug effects , Erythroid Precursor Cells/cytology , Hydrocortisone/pharmacology , Adult , Aged , Aged, 80 and over , Culture Media, Conditioned/pharmacology , Female , Humans , In Vitro Techniques , Lymphocytes , MaleABSTRACT
Blood T lymphocyte subsets have been studied using monoclonal antibodies in 10 chronic uremic patients treated with maintenance hemodialysis. Both total T lymphocytes identified by the antibody OKT3, and the helper-inducer T lymphocyte subset identified by the antibody OKT4 were found to be significantly lower than normal. The cytotoxic-suppressor T cell subset was only moderately, even if significantly reduced, so that the T4/T8 ratio in uremic patients was significantly lower than normal. These data provide an additional contribution to the interpretation of immunological and hematological deficiencies observed in chronic uremia.
Subject(s)
Kidney Diseases/immunology , T-Lymphocyte Subsets/immunology , Uremia/immunology , Adult , Female , Humans , Leukocytes , Lymphocytes , Male , Middle Aged , Renal DialysisABSTRACT
Glucocorticosteroid hormones have been reported either to stimulate or to inhibit human erythropoiesis. We have studied the in vitro effect of hydrocortisone, 10(-6) mol/l, on human BFU-E when stimulated by preconstituted burst-promoting activity (BPA) in a medium conditioned by T lymphocytes. Hydrocortisone was found to stimulate BFU-E growth, even at largely suboptimal concentrations of BPA, through hormone receptors, as the effect was blocked by preincubation of BFU-E with equimolar progesterone. The possibility that glucocorticosteroids may increase the number and/or affinity of erythropoietin receptors on BFU-E is discussed. We have also studied the effect of hydrocortisone on the production of BPA by human T lymphocytes stimulated by phytohemagglutinin. Preincubation of T lymphocytes for 1 h with hydrocortisone, 10(-6) mol/l, significantly reduced the BPA of lymphocyte-conditioned medium. Again the inhibition of BPA production was reversed by incubation of lymphocytes with equimolar doses of progesterone. The conflicting results previously reported on the effect of glucocorticosteroids on erythropoiesis may be due in part to the opposing effects of the hormones on BFU-E growth and BPA production. The role hydrocortisone plays in the physiological regulation of human erythropoiesis is at present largely unknown.
Subject(s)
Erythropoiesis/drug effects , Hydrocortisone/pharmacology , Lymphokines/biosynthesis , T-Lymphocytes/metabolism , Colony-Forming Units Assay , Culture Media , Humans , Lymphocyte Depletion , Lymphokines/physiology , Progesterone/pharmacology , Tissue Inhibitor of MetalloproteinasesABSTRACT
The effect of cimetidine, an inhibitor of suppressor T lymphocytes, on the burst-promoting activity (BPA) of normal T lymphocytes has been studied. Cimetidine has been shown to increase the BPA of normal T lymphocytes, both when added to the culture and when T lymphocytes were preincubated for 1 h with it. Cimetidine had no direct effect on the in vitro growth of burst-forming units (BFU-E). Our results show that CD8 suppressor T lymphocytes inhibit the in vitro growth of BFU-E in normal conditions, either directly or through inhibition of BPA of CD4 helper T lymphocytes. Cimetidine has proved to be a useful tool for investigating the hematological role of T-lymphocyte subsets in normal and pathological conditions.
Subject(s)
Cimetidine/pharmacology , T-Lymphocyte Subsets/physiology , T-Lymphocytes/physiology , Analysis of Variance , CD4-CD8 Ratio , Cells, Cultured , Colony-Forming Units Assay , Culture Media , Humans , Reference Values , T-Lymphocyte Subsets/drug effects , T-Lymphocytes/drug effectsABSTRACT
The effects of uremic serum on the in vitro growth of normal BFU-E and on the burst-promoting activity by normal T-lymphocytes were evaluated separately. The effect of hemodialysis on the removal of possible serum inhibitor(s) was also tested. Sera of 12 uremic patients were shown to provoke a 60% inhibition of the in vitro growth of normal BFU-E and almost complete abolition of burst-promoting activity by T lymphocytes. While hemodialysis significantly removed the inhibition of uremic sera on BFU-E growth, it was rather ineffective in removing the inhibitor(s) of T lymphocytes. The different effects of uremic serum on BFU-E and on T lymphocytes are discussed.
Subject(s)
Erythroid Precursor Cells/cytology , Renal Dialysis , T-Lymphocytes/physiology , Uremia/blood , Adult , Aged , Cell Division , Cell Separation/methods , Chronic Disease , Colony-Forming Units Assay/methods , Female , Humans , Kidney Failure, Chronic/blood , Male , Middle Aged , Uremia/therapyABSTRACT
Erythroid stem cell proliferation is regulated by lymphokines and erythropoietin. The helper subset of T lymphocytes is known to produce the erythroid growth factor IL-3 or burst-promoting activity (BPA), while the suppressor subset seems to inhibit the erythroid growth. Leukocyte-conditioned media derived from white cells of nonanemic elderly were reported to provide defective support to the erythropoiesis. In two groups of elderly, nonanemic and anemic, we studied the ability of T lymphocytes to stimulate the BFU-E growth and the in vitro effect of cimetidine, as a drug that inhibits the suppressor T lymphocytes. Culture data were then compared with the peripheral blood lymphocyte picture. The study shows that defective mononuclear cell support to the BFU-E growth, namely due to reduced absolute number of the T4 subset of T lymphocytes, can be observed in both anemic and nonanemic elderly. It is suggested that isolated defective BPA production is not always sufficient to induce anemia. In most cases, anemia of unexplained origin in senescence would be due to the concomitance of both BFU-E impairment and defective BPA production. The simultaneous evaluation of BFU-E growth, lymphokine production, and the T-lymphocyte blood picture offers the best way to investigate the erythropoiesis of the elderly.
Subject(s)
Aging/metabolism , Anemia/metabolism , Interleukin-3/metabolism , T-Lymphocytes/metabolism , Aged , Aged, 80 and over , Anemia/blood , Cimetidine/pharmacology , Colony-Forming Units Assay , Erythroid Precursor Cells/drug effects , Erythroid Precursor Cells/pathology , Female , Humans , Leukocyte Count , Male , Monocytes/pathology , Reference Values , T-Lymphocyte Subsets/pathology , T-Lymphocytes/physiologyABSTRACT
En un grupo de 22 pacientes diabeticos de tipo I y II, eutiroideos, se evaluaron una serie de parametros de laboratorio indicativos de la funcion tiroidea (TSH, T4, T4 libre, T3 y T3r), que se correlacionaron con el grado de control metabolico, expresado a traves de la glucemia en ayunas y la HbA1. De acuerdo a los valores de la glucemia, los pacientes se dividieron en 3 grupos; I (glucemias de 150 mg%) o menores II (glucemias entre 151 y 250 mg%); III (glucemias mayores de 250 mg%).Se observaron diferencias significativas entre los 3 grupos para la T3 y la T3r. No hubo diferencias para las TSH, T4 y T4 libre.Resultaron significativas las correlaciones enentre glucemia y T3, entre glucemia y T3r, entre HBA1 y T3 y entre HBA1 y T3r. En 3 pacientes con cetoacidosis la T3 que estuvo en el limite inferior de la normalidad o en el rango del hipotiroidismo, se normalizo al corregirse la alteracion metabolica. La T3r experimento cambios en sentido inverso. La determinacion de T3 no seria un indicador seguro del estado funcional tiroideo en diabeticos mal controlados principalmente en aquellos con cetoacidosis