The immune risk profile is associated with age and gender: findings from three Swedish population studies of individuals 20–100 years of age

Abstract

Earlier we identified an Immune Risk Profile (IRP) of very old individuals, 86-94 years of age, characterised by an inverted CD4/CD8 ratio and associated with persistent cytomegalovirus infection and an increase in the numbers of CD3+CD8+CD28- cells. In the present study we included data from a population-based sample in the age range of 20-79 years to examine the prevalence of individuals with an inverted CD4/CD8 ratio relative to age and gender across the entire adult lifespan. Immunological monitoring that was conducted included analysis of the numbers of T-cells in the subsets CD3+, CD3+CD4+, and CD3+CD8+ as well as CD3+CD8+CD28+, CD3+CD8+CD28-, and CD8+CD45RA+CCR7+. There was found to be a significant lowering of the numbers of CD3+, CD3+CD4+, and CD3+CD8+, and of the CD8+CD45RA+CCR7+ cells across the adult life-span. Notably, the prevalence of individuals with an inverted CD4/CD8 ratio increased from about 8% in the age range of 20-59 years to about 16% in the age range of 60-94 years. The mortality rate in individuals with an inverted CD4/CD8 ratio also increased significantly above the age of 60. Interestingly, the proportion of individuals with an inverted CD4/CD8 ratio was found to be significantly higher in men, whereas the numbers of CD3+CD4+ helper and CD8+CD45RA+CCR7+ naïve cells and the CD4/CD8 ratio were found to be significantly higher in women. These results highlight the importance of functioning of the thymus in the development of IRP and may partly account for the differences between sexes in terms of longevity.

Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans

“…In this line, the immune risk profile (IRP) describes a collection of immune-related defects that characterize the immunosenescence (Ferguson et al 1995). The IRP is characterized by an increase in the numbers of CD3+CD8+CD28− cells that result in an inverted CD4:CD8 T cell ratio and is associated with persistent cytomegalovirus infection (Pawelec et al 2005;Wikby et al 2008). In the Swedish cohort, the inversion of the CD4:CD8 T cell ratio in peripheral blood was independently associated with mortality (Wikby et al 1998), providing suggestion-albeit not formal proof-that loss of thymic function could be associated with aging and mortality.…”

Reversing T cell immunosenescence: why, who, and how

“…This concept lends itself to the argument that immunosenescence is not merely a measurement of chronological age but points towards immune exhaustion arising at different ages (i.e., physiological age) (Lang et al 2010b;Mitchell et al 2010). The downward trajectory of an individual's thymic output profile over time has been demonstrated previously by Kilpatrick et al (2008) and could be considered as part of longitudinal studies similar to the OCTA and NONA studies to investigate further the potential role of sj-TREC as predictive marker of aging (Wikby et al 2005;Strindhall et al 2007;Wikby et al 2008). Thus, whether predicting human phenotypes from genotypes is relevant both for personalized medicine and applying preventive strategies (Janssens and van Duijn 2008), additional clinical and translational studies at population, clinical, cellular, and molecular levels are still needed in order to elucidate the exact implications of the TREC values on the age-related senescence of the cell-mediated immune response (Lang et al 2011a).…”

“…Since the single preceding event in all cases of immunosenescence is thymic involution ), can we identify a specific T cell-mediated immunity makers which are linked to a state of immunosenescence? The pioneering OCTO and NONA studies have resulted in the emerging concept of an immune risk profile (IRP) (Wikby et al 2005;Strindhall et al 2007;Wikby et al 2008). This immune condition consists of (1) ) T cells, and T cell proliferative index.…”

Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity

“…Most focus has been on T cells where an accumulation of terminally differentiated CD8 + cells is seen in a subgroup of elderly. The expansion of CD8 T cells is tightly linked to past CMV infection and has been associated with short-term mortality (Ferguson et al 1995;Wikby et al 1998Wikby et al , 2002Wikby et al , 2008. A CMV-driven expansion of CD8 T cells, resulting in an inverted CD4/CD8 ratio, has also been demonstrated in other cohorts, such as patients with common variable immune deficiency (Marashi et al 2012).…”