Purpose of review: With progressive age, the immune system and the propensity for abnormal immunity change fundamentally. Individuals greater than 50 years of age are not only more susceptible to infection and cancer, but also at higher risk for chronic inflammation and immune-mediated tissue damage. The process of immunosenescence is accelerated in rheumatoid arthritis (RA).
Recent findings: Premature T-cell senescence occurs not only in RA, but also has been involved in morbidity and mortality of chronic HIV infection. Senescent cells acquire the 'senescence-associated secretory phenotype', which promotes and sustains tissue inflammation. Molecular mechanisms underlying T-cell aging are beginning to be understood. In addition to the contraction of T-cell diversity because of uneven clonal expansion, senescent T cells have defects in balancing cytoplasmic kinase and phosphatase activities, changing their activation thresholds. Also, leakiness in repairing DNA lesions and uncapped telomeres imposes genomic stress. Age-induced changes in the tissue microenvironment may alter the T-cell responses.
Summary: Gain-of-function and loss-of-function in senescent T cells undermine protective immunity and create the conditions for chronic tissue inflammation, a combination typically encountered in RA. Genetic programs involved in T-cell signaling and DNA repair are of high interest in the search for underlying molecular defects.