In immunology, the discovery of regulatory T (Treg) cells was a major breakthrough. Treg cells play a key role in pregnancy maintenance, in the prevention of autoimmune responses, and in the control of all immune responses, including responses to self cells, cancer, infection, and a transplant. It is currently unclear whether Treg cells are capable of long-term memory of an encounter with an antigen. Although the term “immunological memory” usually means an enhanced ability to protect the body from reinfection, the memory of the suppressive activity of Treg cells helps to avoid the state of generalized immunosuppression that may result from the second activation of the immune system. In this review, we would like to discuss the concept of regulatory memory and in which tissues memory Treg cells can perform their functions.

Aim. The purpose of the study is to establish the level of anxiety and indicators of the cardio-vascular system in athletes of various qualifications. Materials and methods. The study involved 241 athletes aged 14-30 years of various qualifications and sports. To assess personal and situational anxiety, the Spielberger – Khanin state-trait anxiety inventory was used. The obtained indicators of the cardiovascular system were compared with the reference values. Results. For all athletes of various sports, the moderate type of situational and personal anxiety prevailed. Highly skilled athletes distinguished a group of athletes with high situational and personal anxiety. Arterial hypertension in athletes of cyclic sports and martial arts is more physiological in nature. In athletes of speed-strength and reactive-strength sports, myocardial wall is thickened due to fibrotic changes. Conclusion. A different level and type of sports activity affects differently the indicators of the cardiovascular system. It was revealed that the level of anxiety affects the physical preparation of athletes for the competitive period.

Получение и характеристика стабильных антиген-специфических Т-регуляторных клеток с помощью блокаторов циклин-зависимых киназ

Background . Nonspecific immunosuppressive therapy for graft rejection and graft‐versus‐host disease (GVHD) is often accompanied by severe side effects such as opportunistic infections and cancers. Several approaches have been developed to suppress transplantation reactions using tolerogenic cells, including induction of FoxP3 ⁺ Tregs with antigen‐loaded dendritic cells (DCs) and induction of CD4 ⁺ IL‐10 ⁺ cells with interleukin IL‐10‐producing DCs. Here, we assessed the effectiveness of both approaches in the suppression of graft rejection and GVHD. Methods . IL‐10‐producing DCs were generated by the transfection of DCs with DNA constructs encoding mouse IL‐10. Antigen‐loaded DCs from C57BL/6 mice were generated by transfection with DNA constructs encoding antigenic determinants from the H2 locus of CBA mice which differ from the homologous antigenic determinants of C57BL/6 mice. Results . We found that both IL‐10‐producing DCs and antigen‐loaded immature DCs could suppress graft rejection and GVHD but through distinct nonspecific and antigen‐specific mechanisms, respectively. Discussion . We provide data that the novel approach for DCs antigen loading using DNA constructs encoding distinct homologous determinants derived from major histocompatibility complex genes is effective in antigen‐specific suppression of transplantation reactions. Such an approach eliminates the necessity of donor material use and may be useful in immunosuppressive therapy side effects prevention.

Allorecognition is known to involve a large number of lymphocytes carrying diverse T-cell receptor repertoire. Thus, one way to understand allorecognition and rejection mechanisms is via high-throughput sequencing of T-cell receptors. In this study, in order to explore and systematize the properties of the alloreactive T-cell receptor repertoire, we modeled direct and indirect allorecognition pathways using material from inbred mice in vitro and in vivo. Decoding of the obtained T-cell receptor genes using high-throughput sequencing revealed some features of the alloreactive repertoires. Thus, alloreactive T-cell receptor repertoires were characterized by specific V-gene usage patterns, changes in CDR3 loop length, and some amino acid occurrence probabilities in the CDR3 loop. Particularly pronounced changes were observed for directly alloreactive clonotypes. We also revealed a clustering of directly and indirectly alloreactive clonotypes by their ability to bind a single antigen; amino acid patterns of the CDR3 loop of alloreactive clonotypes; and the presence in alloreactive repertoires of clonotypes also associated with infectious, autoimmune, and tumor diseases. The obtained results were determined by the modeling of the simplified allorecognition reaction in inbred mice in which stimulation was performed with a single MHCII molecule. We suppose that the decomposition of the diverse alloreactive TCR repertoire observed in humans with transplants into such simple reactions will help to find alloreactive repertoire features; e.g., a dominant clonotype or V-gene usage pattern, which may be targeted to correct the entire rejection reaction in patients. In this work, we propose several technical ways for such decomposition analysis, including separate modeling of the indirect alloreaction pathway and clustering of alloreactive clonotypes according to their ability to bind a single antigen, among others.

Оценка метаболизма TCR-подобных CAR/CAR/TCR-T-клеток в 3D-культуре