Relationship between Regulatory T Cells and Immune Activation in Human Immunodeficiency Virus-Infected Patients Interrupting Antiretroviral Therapy

Persistent immune activation plays a central role in driving Human Immunodeficiency Virus (HIV) disease progression. Whether CD4+CD25+ regulatory T cells (Tregs) are harmful by suppressing HIV-specific immune responses and/or beneficial through a decrease in immune activation remains debatable. We analysed the relationship between proportion and number of regulatory T cells (Tregs) and immune activation in HIV-infected patients interrupting an effective antiretroviral therapy (ART). Twenty-five patients were included in a substudy of a prospective multicenter trial of treatment interruption (TI) (ANRS 116). Proportions and numbers of Tregs and the proportion of activated CD4 and CD8 T cells were assessed at baseline and month 12 (M12) of TI. Specific anti-HIV CD4 and CD8 responses were investigated at baseline and M12. Non parametric univariate analyses and multivariate linear regression models were conducted. At baseline, the proportion of Tregs negatively correlated with the proportion of HLA-DR+CD8+T cells (r = −0.519). Following TI, the proportion of Tregs increased from 6.3% to 7.2% (p = 0.029); absolute numbers of Tregs decreased. The increase in the proportion of HLA-DR+CD38+CD8+T cells was significantly related to the increase in proportion of Tregs (p = 0.031). At M12, the proportion of Tregs did not negatively correlate with CD8 T-cell activation. Nevertheless, Tregs retain a suppressive function since depletion of Treg-containing CD4+CD25+ cells led to an increase in lymphoproliferative responses in most patients studied. Our data suggest that Tregs are efficient in controlling residual immune activation in patients with ART-mediated viral suppression. However, the insufficient increase in the proportion and/or the decrease in the absolute number of Tregs result in a failure to control immune activation following TI

Объектно-ориентированный подход при решении задачи моделирования физических параметров газоконденсатной смеси в системе трубопроводов

The article states of the example of using the object-oriented approach to modeling of complexly structured objects, in particular the movement of gas-condensate mixture in the piping system-condensate field. Discusses a set of classes that encapsulates the various elements of the network topology and various aspects of the calculated scheme. Shown the advantage of this approach both from the point of view of clarity, and in terms of contextual separation of the functional model.В статье говорится о примере использования возможностей объектно-ориентированного подхода при моделировании сложно структурированных объектов, в частности движения газоконденсатной смеси в системе трубопроводов газоконденсатного месторождения. Рассматриваются набор классов, инкапсулирующих различные элементы топологии сети и различные аспекты расчетной схемы. Показано преимущество данного подхода как с точки зрения наглядности, так и в плане контекстного разделения функционала модели

Анализ математических моделей и методов исследования напряженно- деформированного состояния многослойных конструкций

This article is devoted to the description of the main approaches to mathematical modeling of multilayered plates and covers. The analysis of mathematical models and methods of calculation of multilayered designs is submitted in three directions: the models described about monolayer positions, discrete models and models of layered covers taking into account communications of the contacting layers. Mathematical models and ways of calculation of cylindrical covers are given.Данная статья посвящена описанию основных подходов к математическому моделированию многослойных пластин и оболочек. Анализ математических моделей и методов расчета многослойных конструкций представлен в трех направлениях: модели, описанные с позиции монослоя, дискретные модели и модели слоистых оболочек с учетом связей контактирующих слоев. Приведены математические модели и способы расчета цилиндрических оболочек

Natural antibodies sustain differentiation and maturation of human dendritic cells

The differentiation and maturation of dendritic cells (DCs) is governed by various signals in the microenvironment. Monocytes and DCs circulate in peripheral blood, which contains high levels of natural antibodies (NAbs). NAbs are germ-line-encoded and occur in the absence of deliberate immunization or microbial aggression. To assess the importance of NAbs in the milieu on DC development, we examined the status of DCs in patients with X-linked agammaglobulinemia, a disease characterized by paucity of B cells and circulating antibodies. We demonstrate that the in vitro differentiation of DCs is severely impaired in these patients, at least in part because of low levels of circulating NAbs. We identified NAbs reactive with the CD40 molecule as an important component that participates in the development of DCs. CD40-reactive NAbs restored normal phenotypes of DCs in patients. The maturation process induced by CD40-reactive NAbs was accompanied by an increased IL-10 and decreased IL-12 production. The transcription factor analysis revealed distinct signaling pathways operated by CD40-reactive NAbs compared to those by CD40 ligand. These results suggest that B cells promote bystander DC development through NAbs and the interaction between NAbs and DCs may play a role in steady-state migration of DCs