Cell Rep: Uncover the molecular pathogenes of inhibited T-cells that promote the development of chronic immune diseases in the body

February 16, 2021 // -- The immune system is often depleted in chronic infectious diseases, and scientists from institutions such as the University of Munich in Germany have revealed molecular mechanisms in a study published in the international journal Cell Reports.
T lymphocytes are an important part of the immune system that identifies foreign proteins, known as antigens, such as peptide fragments derived from viruses or cancer cells;
When the virus enters the tissue, T-cells are activated and eliminate pathogens; however, if T-cells are exposed to targeted antigens for long periods of time, they function and eventually deplete, and T-cells no longer secrete inflammatory messenger molecules and do not induce more immune responses.
on the other hand, it makes sense to control these cells to avoid damage to the organism, such as HIV, hepatitis virus and cancer cells.
, understanding the immune system's response to such long-term and persistent threats is a major challenge in modern medicine, and it is where T-cell depletion plays a central role.
Photo Source: CC0 Public Domain Many years ago, researcher Reinhard Obst developed an animal model for research, focusing on T-assisted cells that express CD4 marker molecules and form the largest sub-group of T-cell cells, each of which recognizes a given protein fragment as an antigen.
To control the number and duration of specific antigen expression in the model system, the researchers used a special technique to expose genetically modified mice to different doses of antibiotic strong mycomycin, which controls the synthesis of antigens through drinking water, and a different number of antigens that can be presented to T-cells in these animal organisms;
results show that these effects are dose-dependent, and at high doses T cells undergo apoptosis, but at moderate doses, T-cells can survive but quickly lose function.
researchers demonstrated this depletion of T-cells by regulating the level of antigens they encounter.
At low doses, it takes weeks for cells to show signs of decline, and after further study, antigens are then removed so that the cells can partially recover from their depletion, a dynamic regulation that convinces researchers that auxiliary T cells are surprisingly malleable.
researchers point out that the results of this study have found some therapeutic applications, and the results show that a variety of transcription factors and signaling pathlines can regulate the inactoring state of cells.
Two years ago, several research groups discovered a transcription factor called Tox, which causes the failure of the substitlion of T-cell killer cells; when the Tox gene is removed, T-cell killer cells are less likely to be depleted in chronic infections, effectively protecting against a long-standing virus and, likewise, attacking the organs of host animals.
this paper show that there are many mechanisms that can help regulate T-assisted cells to dynamically adapt to different antigen loads.
researcher Obst hopes to identify specific molecules that inhibit transcription factors or signaling path pathlines that promote T-cell depletion, and the findings are expected to help develop new therapeutic measures to support T-cells' ability to fight chronic infections and cancers, thereby enhancing the body's natural defenses against certain diseases.
() Original source: Anne Trefzer, Pallavi Kadam, Shu-Hung Wang, et al. Dynamic adoption of anergy by antigen-exhausted CD4+ T cells, Cell Reports (2021). DOI: 10.1016/j.celrep.2021.108748