http://www.immunology.umn.edu/sites/immunology.umn.edu/files/1-s2.0-s0092867414015906-main.pdf

Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences

Aging is associated with a dysregulation of the immune response, loosely termed “immunosenescence”. Each part of the immune system is influenced to some extent by the aging process. However, adaptive immunity seems more extensively affected and among all participating cells it is the T cells that are most altered. There is a large body of experimental work devoted to the investigation of age-associated differences in T cell phenotypes and functions in young and old individuals, but few longitudinal studies in humans actually delineating changes at the level of the individual. In most studies, the number and proportion of late-differentiated T cells, especially CD8+ T cells, is reported to be higher in the elderly than in the young. Limited longitudinal studies suggest that accumulation of these cells is a dynamic process and does indeed represent an age-associated change. Accumulations of such late-stage cells may contribute to the enhanced systemic pro-inflammatory milieu commonly seen in older people. We do not know exactly what causes these observed changes, but an understanding of the possible causes is now beginning to emerge. A favored hypothesis is that these events are at least partly due to the effects of the maintenance of essential immune surveillance against persistent viral infections, notably Cytomegalovirus (CMV), which may exhaust the immune system over time. It is still a matter of debate as to whether these changes are compensatory and beneficial or pathological and detrimental to the proper functioning of the immune system and whether they impact longevity. Here, we will review present knowledge of T cell changes with aging and their relation to chronic viral and possibly other persistent infections.

/pdf/human-t-cell-aging-and-the-impact-of-persistent-viral-jv7r7ommzd.pdf

Human T Cell Aging and the Impact of Persistent Viral Infections

Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome). Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina). A myriad of clinical changes, including a basal proinflammatory state (inflamm-aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging. Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long-term care settings), and basal level of inflammation. Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease. Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging.

/pdf/the-microbiota-and-microbiome-in-aging-potential-23hpsdhicb.pdf

The microbiota and microbiome in aging: potential implications in health and age-related diseases

The course of immune maturation has evolved to favour survival at each stage of development in early life. Fetal and neonatal immune adaptations facilitate intrauterine survival and provide early postnatal protection against extracellular pathogens, but they leave infants susceptible to intracellular pathogens such as viruses that are acquired perinatally. This Review focuses on three such pathogens--HIV, hepatitis B virus and cytomegalovirus--and relates the differential impact of these infections in infants and adults to the antiviral immunity that is generated at different ages. A better understanding of age-specific antiviral immunity may inform the development of integrated prevention, treatment and vaccine strategies to minimize the global disease burden resulting from these infections.

/pdf/the-impact-of-differential-antiviral-immunity-in-children-3soyy3i87c.pdf

The impact of differential antiviral immunity in children and adults.

Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates "immunosenescence". This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop.

/pdf/cmv-and-immunosenescence-from-basics-to-clinics-3emf8vnq8l.pdf

CMV and Immunosenescence: from basics to clinics

The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion.

/pdf/report-from-the-second-cytomegalovirus-and-immunosenescence-2i257ovg34.pdf

Report from the second cytomegalovirus and immunosenescence workshop

Compositions and methods are provided for diagnosis and treatment of rheumatoid arthritis. Defects in T cell receptor signaling lower the activation threshold of RA T cells, thus predisposing for a failure in maintenance of immune tolerance. Overexpression of B-Raf and/or K-Ras in CD4 T cells lowers the threshold to respond to TCR triggering in the absence of costimulation and increases responses to citrullinated peptides and other autoantigens.

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Report from the second cytomegalovirus and immunosenescence workshop

Biomarkers for the Diagnosis of Autoimmune Disease