Age-Dependent Changes in Regulatory T Lymphocyte Development and Function: A Mini-Review

Abstract

The generation and function of immuno-suppressive regulatory T lymphocytes (Treg), which can differentiate in the thymus (tTreg) or in the periphery (pTreg), are regulated in an age-dependent manner. tTreg are produced at high levels in the first weeks of age, when they expand and colonize secondary lymphoid organs and peripheral tissues to protect the organism from autoimmune diseases and to promote tissue repair. Once this population of Treg is operational in the periphery, at puberty, thymic output of Treg declines, but self-reactive tTreg generated early on in life are maintained over time and play a major role in preserving homeostasis of the immune system. Extra-thymic pTreg differentiation declines later on in life. pTreg generated throughout life mainly protect the organism from chronic inflammation and the semi-allogeneic fetus from rejection. In this review, age-dependent modulation of the production and function of these two populations of Treg is described.

More that ACE2? NRP1 may play a central role in the underlying pathophysiological mechanism of olfactory dysfunction in COVID-19 and its association with enhanced survival

“…Amongst other immune cells, NRP1 is expressed by regulatory T cells and appears to exert an immunosuppressive effect – perhaps those most susceptible to NRP1 mediated olfactory loss due to higher expression are at the same time better equipped to suppress the cytotoxic storm that is seen in COVID-19, through activation of regulatory T cells? Production of regulatory T cells declines with age [25] , and are down-regulated in obesity [26] . Racial variation in T-cell function has also been described; while higher rates of malignancy described in African-Americans is multifactorial [27] , they have been shown to have higher levels of T helpers cells and lower levels of regulatory T cells – the same variation could contribute to higher mortality from a cytokine storm in COVID-19.…”

The Immunology of Wild Rodents: Current Status and Future Prospects

“…It is also important to remember that these functional immune responses are, at least in part, measures of the influence of immunoregulatory processes. There is evidence from studies in humans that immunoregulatory mechanisms accrue over the life course and in response to microbial exposure, for example, by the accumulation of regulatory T cells ( 37 , 38 ), though the relevance of age-dependent effects in laboratory rodents to those of wild rodents which are typically short lived ( 16 , 32 ) remains unclear. We therefore need to be mindful that while one can measure many immune parameters, these represent different, discrete aspects of the functioning immune system, ranging from frontline effector responses against a pathogen, to back-room regulatory processes.…”

COVID-19: the role of excessive cytokine release and potential ACE2 down-regulation in promoting hypercoagulable state associated with severe illness

“…Age and human leucocyte antigen (HLA) polymorphisms can be factors that predispose COVID-19 patients to prolonged and excessive inflammations. An aged immune system is not only associated with a decreased efficiency for virus clearance due to declined B and T cell productions and functions, leading to constant viral exposure and excessive inflammations, but also associated with an increased propensity for excessive pro-inflammatory cytokine release because of reduced productions of the immunosuppressive thymus-derived regulatory T cells (Tregs) [ 27 , 28 ]. Additionally, HLA displays extensive polymorphisms, and is crucial for the immune response to viral antigens.…”