Homeostatic proliferation as a physiological process and a risk factor for autoimmune pathology

The most important functions of the immune system are the guarantee of multicellularity, the maintenance of genetic homeostasis, and the protection of the organism from various infectious agents. The maintenance of homeostasis within the immune system also plays an important role in the normal functioning of the organism and is realized through several mechanisms. For example, after the resolution of the immune response, the excessive amount of lymphocytes is eliminated via apoptosis due to the competition for the survival factors and because of the lack of specific stimulation, and the excessive amount of antibodies is corrected by idiotype-anti-idiotype interactions. The restoration and maintenance of the lymphocyte count are performed due to the migration from the bone marrow and thymus and the process of homeostatic proliferation that plays the most important role (after the involution of the thymus) for T-lymphocytes. Because of the non-uniformity of the definitions that are met in the published literature, the authors provide the definition of the process of homeostatic proliferation of T-lymphocytes that will be used further in the text. Homeostatic proliferation (HP) is a physiological process to restoration of the peripheral T-lymphocyte pool after lymphopenia of any etiology through the antigen-specific proliferation of lymphocytes under the influence of IL-7 and IL-15, which can acquire pathological features depending on the severity of lymphopenia. Homeostatic proliferation can be conventionally divided into a fast and slow type depending on its intensity. Although such division is highly conventional, there are certain physiological peculiarities of fast and slow HP that can influence the functioning of the immune system, change the T-cell receptor landscape, and lead to the development of pathologies. It is worth noting that fast HP predominantly involves memory effector T-cells, while slow HP also influences naive T-cells. In the present review, the authors discuss the most important physiological and pathological aspects of the homeostatic proliferation of T-lymphocytes.

Automated summary

The immune system plays a vital role in ensuring multicellularity, genetic homeostasis, and protection against infectious agents. Maintenance of homeostasis within the immune system is crucial for the normal functioning of the organism and is achieved through various mechanisms like apoptosis and interactions. Additionally, restoration and maintenance of lymphocyte count are key processes for T-lymphocytes, with homeostatic proliferation playing a significant role.