The role of metabolism on regulatory T cell development and its impact in tumor and transplantation immunity.

Regulatory CD4+ T (Treg) cells play a key role in the induction of immune tolerance and in the prevention of autoimmune diseases. Treg cells are defined by the expression of transcription factor FOXP3, which ensures proliferation and induction of the suppressor activity of this cell population. In a tumor microenvironment, after transplantation or during autoimmune diseases, Treg cells can respond to various signals from their environment and this property ensures their suppressor function. Recent studies showed that a metabolic signaling pathway of Treg cells are essential in the control of Treg cell proliferation processes. This review presents the latest research highlights on how the influence of extracellular factors (e.g. nutrients, vitamins and metabolites) as well as intracellular metabolic signaling pathways regulate tissue specificity of Treg cells and heterogeneity of this cell population. Understanding the metabolic regulation of Treg cells should provide new insights into immune homeostasis and disorders along with important therapeutic implications for autoimmune diseases, cancer and other immune-system-mediated disorders.

The Regulatory-T-Cell Memory Phenotype: What We Know.

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.

Dendritic Cells Transfected with MHC Antigenic Determinants of CBA Mice Induce Antigen-Specific Tolerance in C57Bl/6 Mice.

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.