After activation, T lymphocytes restructure their cell surface to form membrane domains at T cell receptor (TCR)-signaling foci and immunological synapses (ISs). To address whether these rearrangements involve alteration in the structure of the plasma membrane bilayer, we used the fluorescent probe Laurdan to visualize its lipid order. We observed a condensation of the plasma membrane at TCR activation sites.
View Article and Find Full Text PDFRecovery of dendritic cells (DCs) and natural killer (NK) cells after allogeneic stem cell transplantation (SCT) is important for allograft responses and antitumor immunity and thus for treatment outcome. Regulation of this regenerative process is not well understood. We investigated the influence of endogenous cytokines on the recovery and diversification of DC and NK cell subsets up to 6 months after SCT.
View Article and Find Full Text PDFThe flt3 ligand (FL) is a growth and differentiation factor for primitive hematopoietic precursors, dendritic cells, and natural killer cells. Human T lymphocytes express FL constitutively, but the cytokine is retained intracellularly within the Golgi complex. FL is mobilized from the cytoplasmic stores and its serum levels are massively increased during the period of bone marrow aplasia after stem cell transplantation (SCT).
View Article and Find Full Text PDFAplastic anaemia (AA) is an immune-mediated bone marrow failure associated with high serum levels of flt3 ligand (FL). We examined expression of the membrane-bound isoform of FL in peripheral blood and bone marrow cells from AA patients at diagnosis (n = 16) and after immunosuppressive (IS) treatment (n = 36). Flow cytometry demonstrated strongly increased FL levels on the cell surface of T lymphocytes in AA relative to normal controls (P < 0.
View Article and Find Full Text PDFDendritic cells (DC) are professional antigen presenting cells (APC) whose proliferation and functional differentiation can be induced by hematopoietic growth factors including GM-CSF and FLT3 ligand (FL). Colorectal cancers are known to be infiltrated by dendritic cells (DC) and neoplastic cells have been shown to produce GM-CSF. In this work we investigated FLT3 ligand (FL) gene expression and protein production in human colorectal cancer cell lines and clinical tumor specimens.
View Article and Find Full Text PDFIn a prospective long-term study on the incidence of paroxysmal nocturnal hemoglobinuria (PNH), 115 consecutive patients with severe aplastic anemia (SAA), 97 treated with antilymphocyte globulin (ALG) and 18 with bone marrow transplantation (BMT), were observed over a period of 4-18 years and tested for the presence of complement-sensitive hematopoietic precursor cells with the bone marrow (BM) sucrose test. Sixteen (14%) of the ALG-treated patients developed clinical signs of PNH between 0.5 and 8 years after treatment.
View Article and Find Full Text PDFHuman umbilical cord blood (CB) has been recognized as a source of hematopoietic stem cells for transplantation. While hematopoietic properties of neonatal CB from full-term pregnancies have been well characterized, little is known about CB from early gestational ages. We analyzed the content and the growth properties of primitive and committed hematopoietic progenitors in preterm CB from second trimester (week 16-28; n = 17) and early third trimester (week 29-34; n = 17) in comparison with term CB (n = 18).
View Article and Find Full Text PDFThe flt3 ligand (FL) is a growth factor for primitive hematopoietic cells. Serum levels of FL are inversely related to the number and proliferative capacity of early hematopoietic progenitors. We sought to elucidate the molecular mechanism underlying this regulation.
View Article and Find Full Text PDFTo determine the value of flt3 ligand (flt3L) in stimulating hematopoiesis in human hypoproliferative bone marrow disorders, we examined its in vitro effect on bone marrow cells from patients with aplastic anemia (AA). Growth response to flt3L, alone and in combination with other hematopoietic growth factors, was investigated in clonogenic methylcellulose assays, in long-term liquid and stroma cultures. Bone marrow cells were derived from 13 AA patients with persisting in vitro growth defect after immunosuppressive treatment and from nine normal bone marrow donors.
View Article and Find Full Text PDF