Biomedical subjects

R Peréz

Publications and source records attributed to R Peréz.

5 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↗

PubMed1989

Arginine vasopressin mediates cardiovascular responses to hypoxemia in fetal sheep.

Acute hypoxemia results in hypertension, bradycardia, and cardiac output redistribution in fetal sheep. The blood flow redistribution is produced by differential changes in vascular resistance of various fetal organs. alpha-Adrenergic activity is one of the few vasoconstrictor mechanisms thus far identified in the hypoxemic fetal sheep. Arginine vasopressin (AVP) is a potent vasoconstrictor in adults. Since AVP administration to the normoxic fetus mimics some of the fetal cardiovascular responses to hypoxemia and fetal plasma AVP levels increase with hypoxemia, we examined the hypothesis that AVP modifies the fetal cardiovascular response to hypoxemia by changing the vascular resistance of some fetal vascular beds. To test this we determined fetal systemic arterial pressure and fetal cardiac output and its distribution during hypoxemia with and without the V1 AVP antagonist d(CH2)5-Tyr(Me)AVP. Fourteen fetal sheep (0.79-0.90 of gestation) were chronically catheterized. Five days after surgery fetal hypoxemia was induced by introducing a mixture of 95% N2-5% CO2 (10-20 l/min) into a maternal tracheal catheter. The hypoxemia was maintained for 40 min. Fetal heart rate, systemic arterial blood pressure, and combined ventricular output and its distribution (radiolabeled microspheres) were measured before hypoxemia, at 20 min of hypoxemia alone, and at 20 min of hypoxemia plus either AVP antagonist (n = 5) or NaCl 0.9% (n = 5, controls). Fetal hypertension and bradycardia were partially reversed after the AVP antagonist administration during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

PubMedDate not supplied

[Presentation of salmonellosis in the Tandil district, Argentina].

From January 1990 to July 1992 a prospective study on the salmonellosis form of presentation, reservoirs and transmission in Tandil was carried out. Forty strains of Salmonella enterica were isolated with the following distribution: 28 humans (17 children and 11 adults), 6 in foods (1 in raw milk, 3 in well water, 1 in home made mayonnaise and 1 in chicken salad) and 6 in animals (1 in cow, 2 in chicken and 2 in calves). Salmonella Enteritidis was the most frequent isolate. Disease was evident only in a few susceptible hosts and the epidemiological chain could not be determined in all the cases.

Adult↗