Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging

Abstract

The interaction between T cells and the central nervous system (CNS) in homeostasis and injury has been recognized being both pathogenic (CD4+ T-helper 1 - Th1, Th17 and γδT) and ameliorative (Th2 and regulatory T cells - Tregs). However, in-depth studies aimed to elucidate the precise in the aged microenvironment and the dichotomous role of Tregs have just begun and many aspects remain unclear. This is due, not only to a mutual dependency and reciprocal causation of alterations and diseases between the nervous and T cell immune systems, but also to an inconsistent aging of the two systems, which dynamically changes with CNS injury/recovery and/or aging process. Cellular immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution - sources of chronic inflammation in the elderly (termed inflammaging), potentially induces an acceleration of brain aging and memory loss. In turn, aging of the brain via neuro-endocrine-immune network drives total body systemic aging, including that of the immune system. Therefore, immunotherapeutics including vaccination and “protective autoimmunity” provide promising means to rejuvenate neuro-inflammatory disorders and repair CNS acute injury and chronic neuro-degeneration. We review the current understanding and recent discoveries linking the aging immune system with CNS injury and neuro-degeneration. Additionally, we discuss potential recovery and rejuvenation strategies, focusing on targeting the aging T cell immune system in an effort to alleviate acute brain injury and chronic neuro-degeneration during aging, via the “thymus-inflammaging-neurodegeneration axis”.

Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain

“…Neural damage in the CNS preferentially involves the activation of the resident glial cells: microglia and astrocytes . However, activated innate immunity in the brain is able to elicit a strong adaptive immunity reaction through accumulation of misfolded proteins inducing neuroinflammation and long‐term, low‐grade sustained inflammatory factors that stimulate chronically both innate and adaptive immunity . In this context, both AD and PD are age‐related neurodegenerative pathologies characterized by accumulation and aggregation of misfolded proteins: the Aβ peptide in the first case and the α‐synuclein in the latter.…”

Conditional silencing of H-2Dbclass I molecule expression on dendritic cells modulates the protective and pathogenic kinetics of virus-antigen specific CD8 T cell responses during Theiler’s Virus infection

“…In addition, these lymphocytes, themselves, can be drivers of neuropathology. Therefore a more robust understanding of how APCS drive this form of immunity could have profound impact on the development of effective therapies as well as limiting toxicities that arise from mobilizing activated effector CD8 T cells into the brain [62, 63]. In furtherance of these goals, we have described herein a cre-recombinase system for the cell-specific deletion of H-2D b on CD11c+ cell populations in C57BL/6 mice.…”

Immune Response in Decompensated Chronic Heart Failure of Ischemic Origin

“…С возрастом, снижение иммуногенности напрямую связано с функциональной активностью тимуса, оказывающего влияние на созревание Т-клеток [17]. У пожилых людей уменьшение пула наивных Т-клеток, и напротив, увеличение пула Т-клеток памяти, таких как CD28null, часто приводит к повышенной восприимчивости к патогенной атаке и последующему развитию сердечной дисфункции [18]. Определяя важность роли Т-клеток в кардиопротекции, образуется значимая мишень для лечения ХСН посредством модуляции адаптивного иммунного ответа [19].…”