Immune Parameters in a Longitudinal Study of a Very Old Population of Swedish People: A Comparison Between Survivors and Nonsurvivors

Abstract

As a part of an ongoing longitudinal investigation, this study examined relationships between survival and selected immune system parameters in a sample (n = 102) of very old individuals (86-92 years at the time of initial immune system data collection). Analyses were performed comparing initial time-point measurements from those individuals who were alive (n = 75) and those who were deceased (n = 27) two years after initial data collection. Immune system measurements consisted of determination of peripheral blood lymphocytes and lymphocyte subsets, as well as T-cell responses to activation by Concanavalin A. Cluster analysis identified a subgroup associated with nonsurvival which indicated characteristics that included: poor T-cell proliferative responses, high CD8 percentages, and low CD4 and CD19 percentages. This multivariate analysis suggested that combinations of immune system parameters predict two-year survival otherwise not apparent when single immune system parameters were evaluated in the elderly.

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).…”

Relationship between functional ability in older people, immune system status, and intensity of response to CMV

“…In agreement, an immune risk profile (IRP) was initially identified in the Swedish OCTO immune longitudinal study using a cluster analysis approach (Ferguson et al 1995). A higher 2-year mortality occurred in a population of very old Swedish individuals who had a high frequency of CD8 T cells, a low frequency of CD4 cells, and a poor proliferative response to Con A.…”

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).…”

“…A subset of the individuals displayed a combination of increased CD8 + T cells and decreased CD4 + T cells together with a poor proliferative response to mitogenic stimulation (Ferguson et al 1995). Longitudinal data showed this pattern to be predictive of increased 2-year all-cause mortality and strongly associated with CMV infection (Ferguson et al 1995;Wikby et al 1998;Olsson et al 2000). This combination of immune parameters has been designated the immune risk profile (IRP), later defined as a CD4/CD8 ratio < 1.0 (Wikby et al 1998).…”