The inverted CD4/CD8 ratio and associated parameters in 66-year-old individuals: the Swedish HEXA immune study

Abstract

The Swedish OCTO and NONA immune longitudinal studies were able to identify and confirm an immune risk profile (IRP) predictive of an increased 2-year mortality in very old individuals, 86–94 years of age. The IRP, was associated with persistent cytomegalovirus infection and characterized by inverted CD4/CD8 ratio and related to expansion of terminally differentiated effector memory T cells (TEMRA phenotype). In the present HEXA immune longitudinal study, we have examined a younger group of elderly individuals (n = 424, 66 years of age) in a population-based sample in the community of Jönköping, Sweden, to examine the relevance of findings previously demonstrated in the very old. Immunological monitoring that was conducted included T cell subsets and CMV-IgG and CMV-IgM serology. The result showed a prevalence of 15 % of individuals with an inverted CD4/CD8 ratio, which was associated with seropositivity to cytomegalovirus and increases in the level of TEMRA cells. The proportion of individuals with an inverted CD4/CD8 ratio was significantly higher in men whereas the numbers of CD3+CD4+ cells were significantly higher in women. In conclusion, these findings are very similar to those previously found by us in the Swedish longitudinal studies, suggesting that an immune profile previously identified in the very old also exists in the present sample of hexagenerians. Therefore, it will be important to examine clinical parameters, including morbidity and mortality, to assess whether the immune profile also is a risk profile associated with higher mortality in this sample of hexagenerians.

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

“…The low CD4/CD8 ratio in this group was mainly due to an increase in CD8 + T cells and was associated with a very high CMV seropositivity rate (94 %), which is in line with our previous results (Olsson et al 2000;Strindhall et al 2013;Wikby et al 2002). As confirmed in this study, the increased number of CD8 + T cells in subjects with CD4/CD8<1 represents an accumulation of highly differentiated memory T cells, and others have shown these cells to be specific for CMV (Hadrup et al 2006;Olsson et al 2000).…”

“…The study population consisted of a subgroup from the Swedish HEXA cohort, which is a population-based sample of 66-year-old inhabitants of the town of Jönköping, Sweden (Strindhall et al 2013). From the original cohort of 424 participants (HEXA-1), 50 subjects with CD4/CD8 ratio less than one and a random selection of individuals with CD4/CD8 ratio more than 1.2 (n=101) were invited to a new sampling (HEXA-2) for further flow cytometry analysis.…”

“…The present study is part of the new populationbased Swedish HEXA Immune Longitudinal Study of 66-year-old individuals, representing an effort to extend the studies of immunosenescence and IRP to the younger elderly (Strindhall et al 2013). In this age group, it is yet uncertain whether an inversed CD4/CD8 ratio corresponds to increased mortality and truly defines an IRP.…”

Moderate and intense exercise lifestyles attenuate the effects of aging on telomere length and the survival and composition of T cell subpopulations

“…The proportion of total T cells was within the normal range (median ≥60 %) in all groups. The CD4/CD8 ratio averaged 2 in the three groups; there were rare individuals who exhibited an inverted ratio (<1.0), one of the parameters of the immune risk profile (Ferguson et al 1995;Strindhall et al 2013). Other age-related changes include the decrease in the pool of antigeninexperienced (naïve) T cells and the concomitant increase in the number of antigen-experienced (memory) T cells, which has been linked to the loss of immunological efficiency of the aged immune system (Pawelec 2014).…”

“…This immune risk profile is characterized by latent CMV infection, inversion of the CD4/CD8 ratio, and expansion of terminally differentiated memory effector T cells, which are T cells that re-express the CD45RA molecule and have a shorter lifespan. This profile was associated with increased mortality within 2 years among older adults (men and women) (Ferguson et al 1995;Strindhall et al 2013). Additionally, aged individuals tend to exhibit a chronic low-grade inflammatory state that has been implicated in the pathogenesis of many age-related diseases (atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes) (Michaud et al 2013).…”