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Biomedical subjects

K Palucka

Publications and source records attributed to K Palucka.

9 recordsLinked to original sources
PubMed2001

Sensing pathogens and tuning immune responses.

The immune system is capable of making qualitatively distinct responses against different microbial infections, and recent advances are starting to reveal how it manages this complex task. An integral component of the immune system is a network of cells known as dendritic cells (DCs), which sense different microbial stimuli and convey this information to lymphocytes. A better understanding of DC biology has allowed a model to be constructed in which the type of immune response to an infection is viewed as a function of several determinants, including the subpopulation of DCs, the nature of the microbe, microbe recognition receptors, and the cytokine microenvironment.

Animals↗
PubMed2000

Dendritic cell based tumor vaccines.

Dendritic cells (DC) constitute a unique system of cells that induce, sustain and regulate immune responses. Distributed as sentinels throughout the body, DC are poised to capture antigen (Ag), migrate to draining lymphoid organs, and, after a process of maturation, select Ag-specific lymphocytes to which they present the processed Ag, thereby inducing immune responses. DC present Ag to CD4(+) T cells which in turn regulate multiple effectors, including CD8(+) cytotoxic T cells, B cells, NK cells, macrophages and eosinophils, all of which contribute to the protective immune responses. Several key features of the DC system may be highlighted: (1) the existence of different DC subsets that share biological functions, yet display unique ones such as polarization of T cell responses towards Type 1 or Type 2 or regulation of B cell responses; (2) the functional specialization of DC according to their differentiation/maturation stages; and (3) the plasticity of DC which is determined by the microenvironment (e.g. cytokines) and may manifest as (i) the final differentiation into either DC (enhanced antigen presentation) or macrophage (enhanced antigen degradation); (ii) the induction of immunity or tolerance; and (iii) the polarization of T cell responses. Because of these unique properties, DC represent both vectors and targets for immunological intervention in numerous diseases and are optimal candidates for vaccination protocols both in cancer and infectious diseases.

Adoptive Transfer↗
PubMed2000

Flt3-ligand and granulocyte colony-stimulating factor mobilize distinct human dendritic cell subsets in vivo.

Dendritic cells (DCs) have a unique ability to stimulate naive T cells. Recent evidence suggests that distinct DC subsets direct different classes of immune responses in vitro and in vivo. In humans, the monocyte-derived CD11c+ DCs induce T cells to produce Th1 cytokines in vitro, whereas the CD11c- plasmacytoid T cell-derived DCs elicit the production of Th2 cytokines. In this paper we report that administration of either Flt3-ligand (FL) or G-CSF to healthy human volunteers dramatically increases distinct DC subsets, or DC precursors, in the blood. FL increases both the CD11c+ DC subset (48-fold) and the CD11c- IL-3R+ DC precursors (13-fold). In contrast, G-CSF only increases the CD11c- precursors (>7-fold). Freshly sorted CD11c+ but not CD11c- cells stimulate CD4+ T cells in an allogeneic MLR, whereas only the CD11c- cells can be induced to secrete high levels of IFN-alpha, in response to influenza virus. CD11c+ and CD11c- cells can mature in vitro with GM-CSF + TNF-alpha or with IL-3 + CD40 ligand, respectively. These two subsets up-regulate MHC class II costimulatory molecules as well as the DC maturation marker DC-lysosome-associated membrane protein, and they stimulate naive, allogeneic CD4+ T cells efficiently. These two DC subsets elicit distinct cytokine profiles in CD4+ T cells, with the CD11c- subset inducing higher levels of the Th2 cytokine IL-10. The differential mobilization of distinct DC subsets or DC precursors by in vivo administration of FL and G-CSF offers a novel strategy to manipulate immune responses in humans.

Adjuvants, Immunologic↗
PubMed2000

Immunobiology of dendritic cells.

Dendritic cells (DCs) are antigen-presenting cells with a unique ability to induce primary immune responses. DCs capture and transfer information from the outside world to the cells of the adaptive immune system. DCs are not only critical for the induction of primary immune responses, but may also be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response. Although our understanding of DC biology is still in its infancy, we are now beginning to use DC-based immunotherapy protocols to elicit immunity against cancer and infectious diseases.

Animals↗
PubMed1999

Dendritic cells: a link between innate and adaptive immunity.

Dendritic cells (DC) constitute a unique system of cells able to induce primary immune responses. As a component of the innate immune system, DC organize and transfer information from the outside world to the cells of the adaptive immune system. DC can induce such contrasting states as active immune responsiveness or immunological tolerance. Recent years have brought a wealth of information regarding DC biology and pathophysiology, that shows the complexity of this cell system. Although our understanding of DC biology is still in its infancy, we are now in a position to use DC-based immunotherapy protocols to treat cancer and infectious diseases.

Dendritic Cells↗
PubMed1998

Generation of dendritic cells from peripheral blood adherent cells in medium with human serum.

Dendritic cells (DC) provide an effective pathway for presenting antigens to T cells, both self-antigens during T-cell development and foreign antigens during immunity. As such, these cells may be promising adjuvants for immunotherapy. Thus, it is important to establish simple and fast method(s) to generate sufficient numbers of human DC in medium free of calf serum so that the cells can be used for both experimental and clinical purposes. In this report, we used peripheral blood adherent cells, without laborious cell purification or depletion, as the starting population and cultured them in medium supplemented with granulocyte/macrophage colony-stimulating factor and interleukin-4. Substantial numbers of cells with the phenotypical and functional characteristics of immature DC were obtained in a 7-day culture. We then compared DC cultured in medium supplemented with either fetal calf serum or pooled human ABRh+ serum and found no difference in cell yields and in their ability to stimulate alloreactive T cells or to present soluble antigens to T cells. Irradiated cells were less efficient than non-irradiated cells in antigen presentation and stimulation of T cells. Finally, we have examined DC with or without additional tumour necrosis factor-alpha treatment and found that antigen-pulsed mature cells could as efficiently present antigen to T cells as did immature cells. This method is suitable for the generation of DC in studies of large clinical materials.

Adult↗
PubMed1996

Levels of mdr1 and mrp mRNA in leukaemic cell populations from patients with acute myelocytic leukaemia are heterogenous and inversely correlated to cellular daunorubicin accumulation.

Multidrug resistance gene (mdrl) expression is associated with a poor prognosis in acute myelocytic leukaemia (AML). Whether expression of the recently described multidrug resistance-associated gene (mrp) has any prognostic importance in AML is still unclear. The aim of the present study was to investigate the functional role of the mdr1 and mrp mRNA levels in peripheral leukaemic cell populations from patients with AML. Peripheral leukaemic cells from 10 patients with AML were incubated with daunorubicin (DNR). Cellular DNR content was analysed with a fluorescence-activated cell sorter (FACS). From each cell population the 20-25% cells with the lowest and highest DNR content were sorted out, and mdr1 and mrp RNA were quantified in these subpopulations with competitive polymerase chain reaction. The ratio between the mean DNR content in the cell populations with high and low DNR content varied between 1.9 and 6.6. the cell fraction with low DNR content had higher (3.8-40 times)mdr1 mRNA levels in 10/10 patients and higher (1.4-26 times) mrp mRNA levels in 8/10, as compared to the cell fraction with high DNR accumulation. In conclusion, mdr1 and mrp mRNA expressions are heterogenous in leukaemic cell populations from patients with AML. The mdr1 expression, and to some extent mrp expression, is inversely correlated to DNR accumulation in vitro.

Adult↗