Biomedical subjects

K León

Publications and source records attributed to K León.

4 recordsLinked to original sources

PubMed2001

Three-cell interactions in T cell-mediated suppression? A mathematical analysis of its quantitative implications.

Aiming to further our understanding of T cell-mediated suppression, we investigate the plausibility of the hypothesis that regulatory T cells suppress other T cells (target cells), while both cells are conjugated with one APC. We use a mathematical model to analyze the proliferation inhibition scored during in vitro suppression assays. This model is a radical simplification of cell culture reality, assuming that thymidine incorporation is proportional to the number of target cells that would instantaneously form conjugates with APCs that are free of regulatory cells. According to this model the inhibition index should be mainly determined by the number of regulatory cells per APC and should be insensitive to the number of target cells. We reanalyzed several published data sets, confirming this expectation. Furthermore, we demonstrate that the instantaneous inhibition index has an absolute limit as a function of the number of regulatory cells per APC. By calculating this limit we find that the model can explain the data under two non-mutually exclusive conditions. First, only approximately 15% of APCs used in the suppression assays form conjugates with T cells. Second, the growth of the regulatory cell population depends on the target cells, such that the number of regulatory cells per APC increases when they are cocultured with target cells and overcomes its limit. However, if neither of these testable conditions is fulfilled, then one could conclude that suppression in vitro does not require the formation of multicellular conjugates.

Animals↗

PubMed2000

Modelling T-cell-mediated suppression dependent on interactions in multicellular conjugates.

Tolerance to peripheral body antigens involves multiple mechanisms, namely T-cell-mediated suppression of potentially autoimmune cells. Recent in vivo and in vitro evidence indicates that regulatory T cells suppress the response of effector T cells by a mechanism that requires the simultaneous conjugation of regulatory and effector T cells with the same antigen-presenting cell (APC). Despite this strong requirement, it is not yet clear what happens while both cells are conjugated. Several hypotheses are discussed in the literature. Suppression may result from simple competition of regulatory and effector cells for activation resources on the APC; regulatory T cells may deliver an inhibitory signal to effector T cells in the same conjugate; or effector T cells may acquire the regulatory phenotype during their interaction with regulatory T cells. The present article tries to further our understanding of T-cell-mediated suppression, and to narrow-down the number of candidate mechanisms. We propose the first general formalism describing the formation of multicellular conjugates of T cells and APCs. Using this formalism we derive three particular models, representing alternative mechanisms of T-cell-mediated suppression. For each model, we make phase plane and bifurcation analysis, and identify their pros and cons in terms of the relationship with the large body of experimental observations on T-cell-mediated suppression. We argue that accounting for the quantitative details of adoptive transfers of tolerance requires models with bistable regimes in which either regulatory cells or effectors cells dominate the steady state. From this analysis, we conclude that the most plausible mechanism of T-cell-mediated suppression requires that regulatory T cells actively inhibit the growth of effector T cells, and that the maintenance of the population of regulatory T cells is dependent on the effector T cells. The regulatory T cell population may depend on a growth factor produced by effector T cells and/or on a continuous differentiation of effector cells to the regulatory phenotype.

Antigen-Presenting Cells↗

PubMed1998

Natural and induced tolerance in an immune network model.

It has been proposed that the immune system can be partitioned into central and peripheral immune systems. Recently, Carneiro et al. (1996a, b) proposed a network, model incorporating B and T lymphocytes that explicitly accounts for that partition. This model however, had some limitations that are tackled here. Two main changes were introduced: the average idiotypic connectivity is now an explicit function of time based on empirical evidence; and the activation of T lymphocytes by antigen is described by a log-bell shaped dose response curve. The new model, which also accounts for the CIS and PIS distinction, shows more reasonable results since the frequencies of tolerant, immune or autoimmune responses to an antigen are now correct. The model provides a new interpretation for tolerance induction during the neonatal period, and for the adult tolerance by low or high doses of antigen. It predicts that natural tolerance for antigens available during the neonatal period can be kept indefinitely upon their removal, while tolerance induced in the adult stages is rapidly lost upon transient removal of the antigen. A semiquantitative analysis of the model provides a simple explanation for the different results in terms of the frequency at which a limited set of canonical connectivity structures emerge during ontogenesis.

Animals↗

PubMedDate not supplied

[Mucocele of the vermiform appendix].

BACKGROUND: Mucocele is a cystic dilatation of the vermiform appendix that contains mucous material. It may be caused by benign or malignant diseases. AIM: To report and discuss four cases with mucocele. REPORT OF CASES: The main clinical manifestations were abdominal pain and changes in the bowel habits. In two cases, appendiceal mucocele was an incidental finding in the diagnostic work-up or operation for acute diverticulitis and acute cholecystitis, respectively. The diagnostic approach included barium enema and CT scan of the abdomen. In three cases, the mucocele was secondary to mucinous cystadenoma; two of them had a preoperative diagnosis of mucocele and underwent colonic preparation and right hemicolectomy, one patient underwent appendectomy alone. The remaining case underwent appendectomy alone, was found to have mucinous adenocarcinoma, and underwent a right hemicolectomy in a second operation. Postoperative outcome was adequate in all cases. CONCLUSION: Mucocele of the vermiform appendix is a rare disease. An appendectomy is an adequate treatment for benign disease. If malignant disease is demonstrated, a right hemicolectomy should be performed.

Adult↗