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M de Smedt

Publications and source records attributed to M de Smedt.

10 recordsLinked to original sources
PubMed1996

Differential effects of interleukin-15 and interleukin-2 on differentiation of bipotential T/natural killer progenitor cells.

Bipotential T/natural killer (NK) progenitor cells are destined to differentiate mainly into T cell receptor (TCR) alpha beta and TCR gamma delta cells in a thymic microenvironment, whereas extrathymically they selectively develop into NK cells. The exact environmental conditions that are required for differentiation into these three leukocyte populations are largely unknown. In this report, we have investigated and compared the effect of interleukin (IL)-15 and IL-2 in this process. The IL-15 receptor is composed of the gamma and beta chains of the IL-2 receptor (IL-2R gamma and IL-2R beta) and of a specific alpha chain (IL-15R alpha). Here, it is shown that IL-15 mRNA is mainly expressed in thymic epithelial stromal cells, whereas IL-2 mRNA is exclusively expressed in thymocytes. IL-2R beta-expressing cells were present in the fetal thymus with a CD25-CD44+Fc gamma R+HSA-/low TCR- phenotype, which is characteristic of progenitor cells. These cells also expressed IL-15R alpha messenger RNA. Sorted IL-2R beta + TCR- cells differentiated into TCR alpha beta and TCR gamma delta cells after transfer to alymphoid thymic lobes, whereas culture of the same sorted cells in cell suspension in the presence of IL-15 resulted in the generation of functional NK cells. This shows that IL-2R beta +TCR- cells of the fetal thymus contain bipotential T/NK progenitors. Addition of low concentrations of IL-15 to fetal thymic organ culture (FTOC) resulted in an increase of all T cell subpopulations. The largest expansion occurred in the TCR gamma delta compartment. In contrast, low concentrations of IL-2 did not result in a higher total cell number and did not induce outgrowth of TCR gamma delta cells. High concentrations of IL-15 blocked TCR alpha beta development and shifted differentiation towards NK cells. Differentiation towards TCR gamma delta cells still proceeded. High concentrations of IL-2 similarly induced development into NK cells, but the cell number was fourfold lower than in IL-15 cultures. Importantly, blocking of IL-2R alpha in IL-2-treated FTOC resulted in a drastic increase in cell number, indicating that IL-2R alpha negatively regulates cell expansion. Collectively, these experiments provide direct evidence that IL-15 and IL-2 differentially affect the differentiation of bipotential T/NK progenitors.

Animals↗
PubMed1994

Drug formularies--good or evil? A view from the EEC.

The use of standard treatment schemes is believed to provide easier, safer, and more rational prescribing of drugs. Provision of neutral information on relative costs and merits of individual therapies may induce physicians to prescribe more rationally and cost effectively. A drug formulary must be developed by using clinical evidence of efficacy, taking into account all available preparations, choosing the most cost effective formulation of the drug, and as far as possible complying with formularies implemented by other health institutions. Planning process and preparation time are fundamental to formulary development work. A restrictive drug policy in the hospital environment will save time in the pharmacy, as fewer drugs are handled, and will improve prescribing as the staff have fewer drugs to familiarize themselves with. The potential benefits from increased generic prescribing, lower stock levels, and closer working relationships between members of the formulary team should all be considered. The benefit of this interdisciplinary approach to drug therapy will be rapidly recognized.

Belgium↗
PubMed1989

Analysis of the cytotoxic function of the thymocytes generated in a 14-day old mouse fetal thymus organ culture with high dose of IL-2.

The target cell specificity of LAK cells generated by addition of rIL-2 to thymic rudiments of 14 day old BALB/C embryo's was compared to the lytic potential of adult BALB/C splenic LAK cells. We used four tumor cell lines as targets, one NK-susceptible (YAC-1) and three NK-resistant tumors (C1300, P815 and EL4), which were all killed by splenic LAK cells. It is shown that fetal thymic LAK cells display a lower lytic activity, while EL4 tumor cells are not killed at all. By elimination of the CD8 positive cells from both the adult splenic and the fetal thymic LAK cells, we demonstrate that the fetal thymic LAK activity is mainly exerted by CD4-CD8- cells, whereas part of the cytotoxicity of splenic LAK cells is due to CD8+ cells.

Animals↗
PubMed1989

Influence of antibodies neutralizing cytokines on murine fetal thymic organ cultures.

The role of cytokines in early T cell development was evaluated in a thymic organ culture system. Fetal thymic lobes from 14 day old mouse embryo's were cultured in the presence of antibodies neutralizing either IL-4, IL6 or TNF. In addition antibodies neutralizing TNF were added to cultures supplemented with human recombinant IL-2. The influence of these different treatments were evaluated by analyzing the different subsets generated after 12 days of culture with a panel of monoclonal antibodies. The antibody treatment did not result in dramatic changes in the cell populations nor did the anti-TNF inhibit the significant changes that are induced by the IL-2 treatment. These results show that based on the cellularity and thymocyte subsets no influence can be shown by inhibiting these cytokines. Other criteria, e.g. repertoire specificity have to be evaluated to address the influence of these treatments on early T cell development.

Animals↗
PubMed1987

Analysis of human prenatal and postnatal thymocytes with the anti-Tac monoclonal antibody and recombinant interleukin-2.

The expression of the interleukin-2 (Il-2) receptor on the cell surface membrane of human prenatal and postnatal thymocytes has been studied by flow cytometry. The in vitro responsiveness of these thymocytes to human recombinant Il-2 (rIl-2) was also studied. Prenatal and postnatal thymocytes contained very few Tac positive cells. The different T cell antigens T6, T3, T4, T8, T9, T10, 3A1 and T11 were expressed by the first trimester of fetal development. Recombinant Il-2 alone was able to induce proliferation of human prenatal and postnatal thymocytes. From this study and data in the literature we conclude that hither-to a thymic precursor cell carrying the interleukin-2 receptor as is the case for the murine thymus has not been found in man.

Antibodies, Monoclonal↗
PubMed1984

Enzyme analysis of autologous rosette-forming cells.

Autologous rosette-forming cells (ARFC) have been considered to be post-thymic precursor cells. Since thymocytes and peripheral T lymphocytes differ considerably in lactate dehydrogenase isoenzyme pattern and in activity of the enzymes of the purine metabolism, we investigated the enzyme profile in the ARFC. The L-lactate: NAD+ oxi-reductase analysis showed an isoenzyme pattern that closely resembled the pattern found in peripheral T lymphocytes and was totally different from the thymocytes. The levels of adenosine deaminase and purine nucleoside phosphorylase were identical to those found in the peripheral T lymphocytes and different from thymocytes. In our hands, the ARFC-enriched suspension contained predominantly OKT4+ and T mu+ lymphocytes. We propose that ARFC are a heterogeneous population encompassing all known subsets and cannot be considered a separate homogeneous entity.

Adenosine Deaminase↗
PubMed1979

Lactate dehydrogenase isoenzyme pattern of the pre-thymic precursor cell.

The thymic cell precursor was obtained from thymic rudiments of 14 day old mouse embryos of strain NMRI. The LDH isoenzyme pattern of this cell population showed a higher LDH-5 activity than the cortical and medullary thymocytes. These results indicate that during the T-cell development, a shift in the pattern occurs towards the LDH-1 end of the spectrum, as described for other murine tissues and cells. As cortical thymocytes contain less LDH-5 activity than the medullary thymocytes, however, the outcome of the latter cells from the former is in conflict with the shift toward the LDH-1 end of the spectrum. On the contrary a relationship whereby cortical and medullary thymocytes are independently derived from the thymic cell percursor, is consistent with the shift toward LDH-1.

Animals↗
PubMed1977

Levamisole versus placebo as an adjunct to primary therapy of laryngopharyngeal epidermoid carcinoma. Evaluation of the immune status.

Twenty-four patients, with a biopsy-proven laryngeal or hypopharyngeal carcinoma, received as an adjunct to their primary treatment (surgery and/or radiotherapy), levamisole (150 mg daily during three consecutive days, every fortnight) or placebo, following a single-blind, but randomized method. At the end of the follow-up, an investigation of the immune status was done, and compared with that of a healthy control-group. It is concluded that the immunity is disturbed in patients with laryngo-pharyngeal cancer, but that this disturbance does not clearly correlate with the clinical state of the disease. Also, the immunological measures did not appear relevant to the significantly favourable effect of levamisole on the prognosis.

Carcinoma, Squamous Cell↗