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W Egner

Publications and source records attributed to W Egner.

28 records · Page 2Linked to original sources
PubMed1993

Identification of potent mixed leukocyte reaction-stimulatory cells in human bone marrow. Putative differentiation stage of human blood dendritic cells.

Dendritic cells (DC) have been isolated from blood, lymphoid tissue, and other tissues, as potential members of a hemopoietic lineage of specialist APC for naive T lymphocyte activation. To define human bone marrow (BM) DC we have attempted to identify allostimulatory cells with DC-like characteristics among human BM mononuclear cells (BMMC) by FACS cell sorting and immunophenotyping, monitoring the APC function of different cell lineages in the human primary MLR. We show that fresh human BM stimulates allogeneic T lymphocytes with an activity equal to or greater than that of peripheral blood. As with DC from other tissue sources, the most potent stimulatory activity was found in the low density BMMC, and these cells, like peripheral blood, stimulated a maximal allogeneic MLR response at days 5 to 6. FACS purification of the allostimulatory population in fresh human BMMC was undertaken by using a wide range of mAb directed against lineage-associated molecules of mature and immature lymphoid, erythroid, and myeloid cells. The most potent constitutive BMMC stimulatory activity was located in the CD3-, CD11b-, CD14-, CD15-, CD16-, CD19-, CD57-, and glycophorin A- population. A mixture of antibodies to these Ag was used to isolate a "mix-negative" BMMC population, which contained the most highly potent MLR-stimulatory cells. Further cytologic and immunophenotypic analysis of this population revealed an enriched population of HLA-DP+, HLA-DQ+, HLA-DR+, and CD45+ cells, with morphologic similarities to the human tonsil and blood DC. These cells were CD4- and CD1a- and were weakly CD33+ (but CD15-), suggesting a possible early myeloid origin distinct from both the committed granulocytic and monocytic lineages. In addition, they lacked both CD10 and CD20, making a lymphoid origin unlikely. Further identification of these putative DC precursors will allow analysis of the early phases of DC hemopoiesis, whereas the characterization of the MLR-stimulatory cells in human BM will be of major importance in the understanding of BM transplant failure and graft-vs-host disease.

Animals↗
PubMed1993

Allostimulatory cells in fresh human blood: heterogeneity in antigen-presenting cell populations.

The relative ability of unmanipulated monocytes, B cells, and dendritic cells (DC) from peripheral blood to stimulate an allogeneic MLR has not been clearly established. We studied the allostimulatory ability of these cell types from minimally manipulated PBMC populations to exclude the induction of stimulatory properties by the complex isolation procedures commonly used to isolate blood DC. Highly purified cell populations were obtained from volunteer donors by immunolabeling PBMC with mAb directed against known lineage-associated markers and separating the positive and negative population on a FACS. These cells were used as stimulators in an allogeneic MLR. The major allostimulatory activity resides in the CD14, CD11b, and CD19 negative fractions. A mixture of antibodies to T, B, NK, monocyte, and FcRIII positive cells was then used to isolate a minor cell population that contained a markedly superstimulatory population of (CD3, CD14, CD16, CD19, and CD57) negative cells. We demonstrate that this activity is constitutive, and is not an artifact of the adherence and in vitro culture steps used in conventional DC purification procedures. We also show by rigorous depletion of the T cell responders that endogenous HLA class II positive cells in the responder population have little role in presenting processed allogeneic antigens during the primary MLR. Monocytes and B cells are stimulators of the allogeneic MLR, but are considerably less potent on a cell for cell basis than the putative DC population. Finally, because human blood and tonsil DC lack detectable CD43 by immunoperoxidase staining, in contrast to monocytes and activated B cells, we examined the ability of CD43 negative and positive cells to stimulate an allogeneic MLR. Similar allostimulatory activity for the human MLR was shown to reside in both the CD43 positive and negative fractions, suggesting that there may be some heterogeneity in the APC population.

Antigens, CD↗
PubMed1992

Hodgkin's disease cell lines: a model for interleukin-1-independent accessory cell function.

The haemopoietic origins of the Hodgkin's disease (HD)-derived cell lines L428, KM-H2 and HDLM-2 remain controversial. Analysis of T-cell receptor (TcR) and Ig rearrangements cannot resolve this, and lineage promiscuity limits the interpretation of isolated surface antigen expression. Nonetheless the cell marker profile of L428 has similarities with human dendritic cells (DC), and L428 strongly stimulates in the mixed leucocyte reaction (MLR). We therefore undertook an extended immunophenotypic comparison of the HD lines with that recently defined for DC, prior to examining their ability to stimulate allogenic T lymphocytes, and comparing the molecular interactions involved with those of primary MLR stimulatory cells. The immunophenotype of the HD lines failed to establish either a lymphoid or monocytoid derivation. The profile of L428 appeared similar to the human DC. All three lines were potent stimulators in the primary MLR, and each expressed relevant adhesion and signal-transducing molecules important for co-stimulating T lymphocytes. Inhibition studies using monoclonal antibodies indicated similar contributions within HD line-T cell MLR to that documented in human tonsil DC-T cell MLR. The HD lines produced no detectable interleukin-1 (IL-1) by biological or immunological analysis. Moreover they stimulated allogeneic T lymphocytes in the presence of anti-IL-1 antibodies. Thus although IL-1 mRNA can be detected in both HDLM-2 and KM-H2 by polymerase chain reaction, these lines, and L428, share with DC the ability to stimulate allogeneic T lymphocytes in an IL-1-independent manner [corrected]. HD lines, particularly L428, may provide a standardized, reproducible, IL-1-independent model for dissection of the co-stimulatory requirements of the human primary MLR.

Antigens, CD↗
PubMed1990

An open study of the efficacy and safety of single dose fosfomycin trometamol in treatment of hospitalised patients with urinary tract infection (pilot study).

Single dose fosfomycin trometamol (3 g) was used to treat 20 hospitalised patients with UTI. Tolerance was good or excellent in 19/20 patients; a satisfactory bacteriological outcome was recorded in 11/17 of patients with sensitive organisms and a satisfactory clinical outcome was noted in 12/16 symptomatic individuals.

Administration, Oral↗
PubMed1990

Titration of antibodies against neutrophil cytoplasmic antigens is useful in monitoring disease activity in systemic vasculitides.

Titration of antibodies against neutrophil cytoplasmic antigens (cANCA), as detected by indirect immunofluorescence, is shown to be clinically useful for monitoring disease activity in Wegener's granulomatosis and microscopic polyarteritis. Ten patients were followed (eight from presentation) prospectively for up to 2 years; during this time there were six episodes of vasculitic relapse in four patients and five infective episodes and one pulmonary embolus in four patients. Titres of cANCA were markedly raised, both at presentation (1/32-1/2048) and at vasculitic relapse (1/125-1/1048) but not in infection or embolism (negative, 1/16). Thus the titre of these antibodies can distinguish nonvasculitic illness from vasculitic relapse, in contrast to C-reactive protein levels which were raised in both. Titres of cANCA fell gradually after vasculitic relapse, in keeping with the half-life of IgG (3 weeks). C-reactive protein is a better measure of recovery.

Adult↗