scholarly journals Abnormal in vitro proliferation and differentiation of T colony-forming cells in patients with lymphadenopathy syndrome

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 1063-1069
Author(s):  
Y Lunardi-Iskandar ◽  
V Georgoulias ◽  
W Rozenbaum ◽  
D Klatzmann ◽  
MC Coll ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Growth Factors ◽  
Peripheral Blood ◽  
Colony Formation ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Interleukin 2 ◽  
Proliferation And Differentiation

Patients with acquired immunodeficiency syndrome (AIDS) present impaired colony growth and in vitro differentiation capacity of peripheral blood and bone marrow T colony-forming cells (T-CFC). We show that peripheral blood, bone marrow, and lymph node T-CFC from patients with persistent lymphadenopathy syndrome (LAS), a syndrome that can precede AIDS, displayed similar abnormalities. Indeed, peripheral blood T-CFC generated a low number of colonies in seven out of 12 patients, and almost no colonies were obtained from bone marrow cells of all patients. The simultaneous study of T-CFC from peripheral blood and lymph node mononuclear cells seems to provide a reliable indicator for the risk of developing AIDS. The six patients who developed AIDS displayed extremely low numbers of peripheral blood T- CFC (13 +/- 17 colonies per 5 X 10(4) cells), and in two of them, no colonies could be obtained from lymph node T-CFC. The remaining patients who had not developed AIDS displayed a higher number of peripheral blood T-CFC (141 +/- 113 per 5 X 10(4) cells) and lymph node T-CFC, which, in addition, preserved their clonogenic capacity. In some patients, peripheral blood and lymph node, but not bone marrow, T-CFC were capable of generating colonies in the absence of added growth factors or mitogens, whereas in others, colony formation was obtained with purified interleukin 2 (IL 2) alone. Both spontaneous and IL 2- induced colony formation was abrogated by a monoclonal antibody against the IL 2 receptor. Taken together, these findings suggest that at least some T-CFC expressed IL 2 receptors. Colonies generated either in the presence or in the absence of added growth factors were composed of T4+, T6+, and T8+ cells, indicating impaired in vitro T-CFC differentiation. These findings indicate that a dramatic quantitative and qualitative impairment of the proliferation and differentiation of peripheral blood and lymph node T-CFC precedes the clinical evolution from LAS to AIDS.

scholarly journals Abnormal in vitro proliferation and differentiation of T colony-forming cells in patients with lymphadenopathy syndrome

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 1063-1069 ◽  
Author(s):  
Y Lunardi-Iskandar ◽  
V Georgoulias ◽  
W Rozenbaum ◽  
D Klatzmann ◽  
MC Coll ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Growth Factors ◽  
Peripheral Blood ◽  
Colony Formation ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Interleukin 2 ◽  
Proliferation And Differentiation

Abstract Patients with acquired immunodeficiency syndrome (AIDS) present impaired colony growth and in vitro differentiation capacity of peripheral blood and bone marrow T colony-forming cells (T-CFC). We show that peripheral blood, bone marrow, and lymph node T-CFC from patients with persistent lymphadenopathy syndrome (LAS), a syndrome that can precede AIDS, displayed similar abnormalities. Indeed, peripheral blood T-CFC generated a low number of colonies in seven out of 12 patients, and almost no colonies were obtained from bone marrow cells of all patients. The simultaneous study of T-CFC from peripheral blood and lymph node mononuclear cells seems to provide a reliable indicator for the risk of developing AIDS. The six patients who developed AIDS displayed extremely low numbers of peripheral blood T- CFC (13 +/- 17 colonies per 5 X 10(4) cells), and in two of them, no colonies could be obtained from lymph node T-CFC. The remaining patients who had not developed AIDS displayed a higher number of peripheral blood T-CFC (141 +/- 113 per 5 X 10(4) cells) and lymph node T-CFC, which, in addition, preserved their clonogenic capacity. In some patients, peripheral blood and lymph node, but not bone marrow, T-CFC were capable of generating colonies in the absence of added growth factors or mitogens, whereas in others, colony formation was obtained with purified interleukin 2 (IL 2) alone. Both spontaneous and IL 2- induced colony formation was abrogated by a monoclonal antibody against the IL 2 receptor. Taken together, these findings suggest that at least some T-CFC expressed IL 2 receptors. Colonies generated either in the presence or in the absence of added growth factors were composed of T4+, T6+, and T8+ cells, indicating impaired in vitro T-CFC differentiation. These findings indicate that a dramatic quantitative and qualitative impairment of the proliferation and differentiation of peripheral blood and lymph node T-CFC precedes the clinical evolution from LAS to AIDS.

scholarly journals Characterization of the potentiation effect of activin on human erythroid colony formation in vitro

Blood ◽  
1989 ◽  
Vol 73 (4) ◽  
pp. 952-960 ◽  
Author(s):  
J Yu ◽  
L Shao ◽  
J Vaughan ◽  
W Vale ◽  
AL Yu
Keyword(s):  
Bone Marrow ◽  
T Lymphocytes ◽  
Dna Synthesis ◽  
Peripheral Blood ◽  
Colony Formation ◽  
Mononuclear Cells ◽  
Erythroid Progenitors ◽  
Potentiation Effect ◽  
Proliferation And Differentiation

Activin, also named FSH-releasing protein, was previously shown to induce hemoglobin accumulation in K562 cells and potentiate the proliferation and differentiation of CFU-E in human bone marrow cultures. Present studies indicate that the potentiation effect of activin is lineage specific. In addition to CFU-E, activin caused an increase in the colony formation of BFU-E from either bone marrow or peripheral blood. It had little effect on the colony formation of CFU- GM and the mixed colonies from CFU-GEMM. In serum-depleted culture, the effect of activin was shown to be dose-dependent with doses effective at picomolar concentrations. The potentiation effect of activin was exerted indirectly through mediation of both monocytes and T lymphocytes. Activin was also found to increase specifically the proportion of DNA-synthesizing erythroid progenitors from both bone marrow and peripheral blood. It had little effect on DNA synthesis in CFU-GM and in mitogen-stimulated lymphocytes. Addition of the monocytes or T lymphocytes to their respective depleted subpopulations of mononuclear cells reconstituted the enhancing effect of activin on the colony formation and DNA synthesis of erythroid progenitors. These results strongly suggest a specific role of activin in potentiating the proliferation and differentiation of erythroid progenitors in vitro.

scholarly journals Characterization of the potentiation effect of activin on human erythroid colony formation in vitro

Blood ◽  
1989 ◽  
Vol 73 (4) ◽  
pp. 952-960 ◽  
Author(s):  
J Yu ◽  
L Shao ◽  
J Vaughan ◽  
W Vale ◽  
AL Yu
Keyword(s):  
Bone Marrow ◽  
T Lymphocytes ◽  
Dna Synthesis ◽  
Peripheral Blood ◽  
Colony Formation ◽  
Mononuclear Cells ◽  
Erythroid Progenitors ◽  
Potentiation Effect ◽  
Proliferation And Differentiation

Abstract Activin, also named FSH-releasing protein, was previously shown to induce hemoglobin accumulation in K562 cells and potentiate the proliferation and differentiation of CFU-E in human bone marrow cultures. Present studies indicate that the potentiation effect of activin is lineage specific. In addition to CFU-E, activin caused an increase in the colony formation of BFU-E from either bone marrow or peripheral blood. It had little effect on the colony formation of CFU- GM and the mixed colonies from CFU-GEMM. In serum-depleted culture, the effect of activin was shown to be dose-dependent with doses effective at picomolar concentrations. The potentiation effect of activin was exerted indirectly through mediation of both monocytes and T lymphocytes. Activin was also found to increase specifically the proportion of DNA-synthesizing erythroid progenitors from both bone marrow and peripheral blood. It had little effect on DNA synthesis in CFU-GM and in mitogen-stimulated lymphocytes. Addition of the monocytes or T lymphocytes to their respective depleted subpopulations of mononuclear cells reconstituted the enhancing effect of activin on the colony formation and DNA synthesis of erythroid progenitors. These results strongly suggest a specific role of activin in potentiating the proliferation and differentiation of erythroid progenitors in vitro.

scholarly journals Acquired amegakaryocytic thrombocytopenic purpura: a syndrome of diverse etiologies

Blood ◽  
1982 ◽  
Vol 60 (5) ◽  
pp. 1173-1178 ◽  
Author(s):  
R Hoffman ◽  
E Bruno ◽  
J Elwell ◽  
E Mazur ◽  
AM Gewirtz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Colony Formation ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Additional Patient ◽  
Platelet Glycoprotein ◽  
Intrinsic Defect ◽  
Thrombocytopenic Purpura ◽  
Marrow Cells

Abstract The possible pathogenetic mechanisms responsible for the production of acquired amegakaryocytic thrombocytopenic purpura (AATP) were investigated in a group of patients with this disorder. Absence of megakaryocytes and small platelet glycoprotein-bearing mononuclear cells, as determined by immunochemical staining of patient marrows with an antisera to platelet glycoproteins, suggested that the defect in AATP occurs in an early progenitor cell of the megakaryocytic lineage. Using an in vitro clonal assay system for negakaryocytic progenitor cells or megakaryocyte colony-forming units (CFU-M), the proliferative capacity of AATP marrow cells was then assessed. Bone marrow cells from three of four patients formed virtually no megakaryocyte colonies, suggesting that in these individuals the AATP was due to an intrinsic defect in the CFU-M. Bone marrow cells from an additional patient, however, formed 12% of the normal numbers of colonies, providing evidence for at least partial integrity of the CFU-M compartment in this patient. Serum specimens from all six patients were screened for their capacity to alter in vitro megakaryocyte colony formation. Five of six sera enhanced colony formation in a stepwise fashion, demonstrating appropriately elevated levels of megakaryocyte colony- stimulating activity. The serum of the patient with partial integrity of the CFU-M compartment, however, stimulated colony formation only at low concentrations. At higher concentrations, this patient's serum actually inhibited the number of colonies cloned, suggesting the presence of a humoral inhibitor to CFU-M. Serum samples from all patients were further screened for such humoral inhibitors of megakaryocyte colony formation using a cytotoxicity assay. The patient whose serum was inhibitory to CFU-M at high concentrations was indeed found to have a complement-dependent serum IgG inhibitor that was cytotoxic to allogeneic and autologous marrow CFU-M but did not alter erythroid colony formation. These-studies suggest that AATP can be due to at least two mechanisms: either an intrinsic effect at the level of the CFU-M or a circulating cytotoxic autoantibody directed against the CFU-M.

Juvenile Chronic Myelogenous Leukemia: Surface Antigen Phenotyping by Monoclonal Antibodies and Cytogenetic Studies

PEDIATRICS ◽  
1986 ◽  
Vol 77 (3) ◽  
pp. 330-335
Author(s):  
Kevin Shannon ◽  
Gabriel Nunez ◽  
Lois W. Dow ◽  
Arthur G. Weinberg ◽  
Yuichi Sato ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Chronic Myelogenous Leukemia ◽  
Chromosomal Abnormality ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Myelogenous Leukemia ◽  
Peripheral Blood Mononuclear

Cells from three children with juvenile chronic myelogenous leukemia were studied using culture in semisolid media, cytogenetic analysis, and surface staining with the monocyte-specific monoclonal antibodies 61D3 and 63D3. The percentage of bone marrow mononuclear cells that were 61D3- and 63D3-positive was markedly increased in all three patients. Bone marrow and peripheral blood mononuclear cells exhibited exceptionally bright immunofluorescence with these antibodies. The presence of monocyte-specific antigens on the surface of juvenile chronic myelogenous leukemia cells suggests that they are derived from a precursor with monocytic characteristics. A specific chromosomal abnormality (47, XY+21) was present in fresh bone marrow cells from one patient; in contrast, 50 metaphases from phytohemagglutinin-stimulated peripheral blood contained a normal karyotype. The chromosomal abnormality was also identified in myeloid colonies grown in vitro from this patient. Granulocytic elements were demonstrated in tissue sections and in cultured myeloid colonies from this child. Our data suggest that malignant transformation in juvenile chronic myelogenous leukemia involves a myeloid progenitor population capable of differentiation in vitro to cells with monocytic or granulocytic characteristics.

scholarly journals Binding of fluorescein-labeled anaphylatoxin C5a to human peripheral blood, spleen, and bone marrow leukocytes

Blood ◽  
1992 ◽  
Vol 79 (1) ◽  
pp. 152-160
Author(s):  
T Werfel ◽  
M Oppermann ◽  
M Schulze ◽  
G Krieger ◽  
M Weber ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Human Peripheral Blood ◽  
Myeloid Cells ◽  
Lymphocyte Subpopulation ◽  
Marrow Cells

The expression of C5a receptors (C5aR) on human leukocytes was evaluated by flow cytometry using fluorescein-labeled human C5a (C5a- F). Granulocytes and CD14+ mononuclear cells (MNL) but not CD3+, CD20+, CD16+, CD56+, or CD11b+ lymphocytes in peripheral blood and spleen bound C5a-F. C5a-F binding was saturable and inhibitable by anti-C5a monoclonal antibody (MoAb) C17/5 or unlabeled C5a. During hemodialysis, which led to the generation of C5a, only granulocytes and monocytes increased their expression of the adhesion molecule CD11b (CR3). In vitro, C5a induced an increase of CR3 and p 150/95 (CD11c/CR4) only on myeloid cells. However, treatment of leukocytes with phorbol 12- myristate 13 acetate increased CR3 and CR4 expression on both myeloid cells and a lymphocyte subpopulation. Stimulation of MNL in mixed lymphocyte cultures or by treatment with conditioned medium or with IFN- gamma did not induce binding sites for C5aR on lymphocytes and reduced the binding of C5a-F to monocytes. The expression of C5aR on low- density bone marrow cells was analyzed by setting appropriate gates during flow cytometry. Cells that bound C5a-F were found in all populations that contained granulocyte and monocyte precursors, but not in lymphocyte precursor populations. All C5aR+ bone marrow cells were CD34 and expressed high levels of CR3, which suggests a late appearance of C5aR during myeloid cell maturation. Our results indicate that C5aR is exclusively expressed on myeloid cells within the hematopoetic cell population.

scholarly journals Acquired amegakaryocytic thrombocytopenic purpura: a syndrome of diverse etiologies

Blood ◽  
1982 ◽  
Vol 60 (5) ◽  
pp. 1173-1178
Author(s):  
R Hoffman ◽  
E Bruno ◽  
J Elwell ◽  
E Mazur ◽  
AM Gewirtz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Colony Formation ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Additional Patient ◽  
Platelet Glycoprotein ◽  
Intrinsic Defect ◽  
Thrombocytopenic Purpura ◽  
Marrow Cells

The possible pathogenetic mechanisms responsible for the production of acquired amegakaryocytic thrombocytopenic purpura (AATP) were investigated in a group of patients with this disorder. Absence of megakaryocytes and small platelet glycoprotein-bearing mononuclear cells, as determined by immunochemical staining of patient marrows with an antisera to platelet glycoproteins, suggested that the defect in AATP occurs in an early progenitor cell of the megakaryocytic lineage. Using an in vitro clonal assay system for negakaryocytic progenitor cells or megakaryocyte colony-forming units (CFU-M), the proliferative capacity of AATP marrow cells was then assessed. Bone marrow cells from three of four patients formed virtually no megakaryocyte colonies, suggesting that in these individuals the AATP was due to an intrinsic defect in the CFU-M. Bone marrow cells from an additional patient, however, formed 12% of the normal numbers of colonies, providing evidence for at least partial integrity of the CFU-M compartment in this patient. Serum specimens from all six patients were screened for their capacity to alter in vitro megakaryocyte colony formation. Five of six sera enhanced colony formation in a stepwise fashion, demonstrating appropriately elevated levels of megakaryocyte colony- stimulating activity. The serum of the patient with partial integrity of the CFU-M compartment, however, stimulated colony formation only at low concentrations. At higher concentrations, this patient's serum actually inhibited the number of colonies cloned, suggesting the presence of a humoral inhibitor to CFU-M. Serum samples from all patients were further screened for such humoral inhibitors of megakaryocyte colony formation using a cytotoxicity assay. The patient whose serum was inhibitory to CFU-M at high concentrations was indeed found to have a complement-dependent serum IgG inhibitor that was cytotoxic to allogeneic and autologous marrow CFU-M but did not alter erythroid colony formation. These-studies suggest that AATP can be due to at least two mechanisms: either an intrinsic effect at the level of the CFU-M or a circulating cytotoxic autoantibody directed against the CFU-M.

scholarly journals Binding of fluorescein-labeled anaphylatoxin C5a to human peripheral blood, spleen, and bone marrow leukocytes

Blood ◽  
1992 ◽  
Vol 79 (1) ◽  
pp. 152-160 ◽  
Author(s):  
T Werfel ◽  
M Oppermann ◽  
M Schulze ◽  
G Krieger ◽  
M Weber ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Human Peripheral Blood ◽  
Myeloid Cells ◽  
Lymphocyte Subpopulation ◽  
Marrow Cells

Abstract The expression of C5a receptors (C5aR) on human leukocytes was evaluated by flow cytometry using fluorescein-labeled human C5a (C5a- F). Granulocytes and CD14+ mononuclear cells (MNL) but not CD3+, CD20+, CD16+, CD56+, or CD11b+ lymphocytes in peripheral blood and spleen bound C5a-F. C5a-F binding was saturable and inhibitable by anti-C5a monoclonal antibody (MoAb) C17/5 or unlabeled C5a. During hemodialysis, which led to the generation of C5a, only granulocytes and monocytes increased their expression of the adhesion molecule CD11b (CR3). In vitro, C5a induced an increase of CR3 and p 150/95 (CD11c/CR4) only on myeloid cells. However, treatment of leukocytes with phorbol 12- myristate 13 acetate increased CR3 and CR4 expression on both myeloid cells and a lymphocyte subpopulation. Stimulation of MNL in mixed lymphocyte cultures or by treatment with conditioned medium or with IFN- gamma did not induce binding sites for C5aR on lymphocytes and reduced the binding of C5a-F to monocytes. The expression of C5aR on low- density bone marrow cells was analyzed by setting appropriate gates during flow cytometry. Cells that bound C5a-F were found in all populations that contained granulocyte and monocyte precursors, but not in lymphocyte precursor populations. All C5aR+ bone marrow cells were CD34 and expressed high levels of CR3, which suggests a late appearance of C5aR during myeloid cell maturation. Our results indicate that C5aR is exclusively expressed on myeloid cells within the hematopoetic cell population.

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