CD8+ T Cell Senescence: Lights and Shadows in Viral Infections, Autoimmune Disorders and Cancer

Abstract

CD8+ T lymphocytes are a heterogeneous class of cells that play a crucial role in the adaptive immune response against pathogens and cancer. During their lifetime, they acquire cytotoxic functions to ensure the clearance of infected or transformed cells and, in addition, they turn into memory lymphocytes, thus providing a long-term protection. During ageing, the thymic involution causes a reduction of circulating T cells and an enrichment of memory cells, partially explaining the lowering of the response towards novel antigens with implications in vaccine efficacy. Moreover, the persistent stimulation by several antigens throughout life favors the switching of CD8+ T cells towards a senescent phenotype contributing to a low-grade inflammation that is a major component of several ageing-related diseases. In genetically predisposed young people, an immunological stress caused by viral infections (e.g., HIV, CMV, SARS-CoV-2), autoimmune disorders or tumor microenvironment (TME) could mimic the ageing status with the consequent acceleration of T cell senescence. This, in turn, exacerbates the inflamed conditions with dramatic effects on the clinical progression of the disease. A better characterization of the phenotype as well as the functions of senescent CD8+ T cells can be pivotal to prevent age-related diseases, to improve vaccine strategies and, possibly, immunotherapies in autoimmune diseases and cancer.

Janus Kinase Inhibitors: A New Tool for the Treatment of Axial Spondyloarthritis

“…The most likely hypothesis to explain the occurrence of axSpA is that the effect of environmental factors together with a genetic predisposition may induce a chronic inflammatory response involving both innate and adaptive immunity [ 15 , 16 , 17 ]. AxSpA is strongly associated with the presence of the HLA-B27 allele, which is very rare in the general population [ 18 , 19 , 20 , 21 ]. However, the mechanism by which this allele may contribute to the pathogenesis of axSpA is still the subject of intensive studies.…”

Multi-omics integrated analysis reveals a specific phenotype of CD8+ T cell may contribute to immunothromosis via Th17 response in severe and critical COVID-19

“…Senescent T cells may damage healthy tissue under severe inflammation caused by COVID-19 [50]. Limiting the expansion or increasing the clearance of senescent CD8+ T cells may be crucial for preventing and ameliorating viral infections, autoimmune disorders and other aging-related diseases [51]. Elderly COVID-19 patients are more likely to accumulate high levels of cellular senescence, leading to uncontrolled SARS-CoV-2-mediated cytokine storms and excessive inflammatory reaction during the early phase of the disease, which in turn promote tissue damage leading to lung failure and multi-tissue dysfunctions, and might negatively impact on vaccine efficacy [52].…”

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“…Long-term alterations are found not only in primary B and T cell functions in COVID-19 patients up to 6 months following hospital discharge [ 156 ] but also in the vast majority of CD4+ T cell and CD8+ T cell subsets that are critical for the control of intracellular and extracellular pathogen infections [ 157 ]. Long-term alterations in maturation and differentiation of NK and CD8+ T cells, linked with high expression of inhibitory receptors and markers of ‘cellular senescence’ on their surface, as well as the low efficiency of target cell elimination can dramatically influence the effectiveness of antitumor immunity [ 158 , 159 , 160 ]. Moreover, alterations in both inflammation and immune responses in the setting of convalescent COVID-19 may influence future risk of various conditions such as cardiovascular, autoimmune, pulmonary, and neurological diseases, etc.…”