The immune risk profile and associated parameters in late life: Lessons from the OCTO and NONA longitudinal studies

Abstract

The OCTO Immune Longitudinal Study is a population-based study of ageing in a sample of 102 Swedish octogenarians with the aim to explore age changes of the immune system using a sample selected for good health. Data collection was performed in 1989, 1990, 1991 and 1997. An Immune Risk Profile (IRP) associated with increased mortality was characterized by high CD8+, low CD4+ T-cell counts and a poor T-cell proliferative response, inversion of the CD4/CD8 ratio and evidence of persistent cytomegalovirus infection was identified. The subsequent NONA Immune Longitudinal Study of 138 Swedish nonagenarians was performed in 1999, 2001, 2003, and 2005, not excluding individuals due to compromised health. The overall aim was to examine predictive factors for longevity and to further investigate in greater depth the immune risk profile identified in the OCTO Immune Study in the context of functional and disability parameters also examined in the NONA. The immune panel included the analysis of T-cell subsets, inflammatory markers, virus serology, cytokines, TCR clonotype mapping, and functional and phenotypic analysis of virus specific CD8+ cells by HLA/peptide multimers, in collaborations between participants of the EU funded T-CIA project. The present chapter report findings from the longitudinal studies of Swedish octo-nonagenarians with focus on IRP and its associations with persistent virus infection, CD8+ T-cell differentiation, cytokines, cognitive functioning, inflammatory activity, virus specific CD8+ cells, CD8+ T-cell clonal expansions and longevity. It also reports on low grade inflammation processes of importance in predicting longevity in the very late life.