Longitudinal studies of clonally expanded CD8 T cells reveal a reperoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly

• The age-associated decrease in functionality of the human immune system is thought to have a negative impact on the capacity to provide protection against infection, in turn leading to in-creased incidence of mortality. In a previous longitudinal study of octogenarians, we identi-fied an immune risk phenotype (IRP) in the very elderly defined by an inverted CD4/CD8 ra-tio, which was associated with increased mortality and persistent CMV infection. In this study, we analyzed the CD8 clonal composition of nonagenarians and middle-aged individu-als. An increased number of CD8 T cell clones was observed in the nonagenarians, and was associated with CMV-seropositivity. Surprisingly, CMV-seropositive nonagenarians with the IRP had a significantly lower number of clones compared with non-IRP individuals. The de-crease in clone numbers in IRP individuals was associated with shorter survival time. MHC/peptide multimer staining indicated that the frequency of CMV-specific T cells was higher in nonagenarians than in the middle-aged, but the ratio of functionally intact cells was significantly lower. The lowest ratio of functional CMV-specific T cells was found in an IRP individual. A thorough longitudinal analysis of the CMV-specific T cells in nonagenarians showed a stable pattern with respect to frequency, phenotype, and clonal composition. We hypothesize that the number of different CD8 T cell clonal expansions increases as the indi-vidual ages, possibly, as a compensatory mechanism to control latent infections, e.g., CMV, but eventually a point is reached where clonal exhaustion leads to shrinkage of the CD8 clonal repertoire, associated with decreased survival

Ämnesord

SAMHÄLLSVETENSKAP  -- Psykologi (hsv//swe)

SOCIAL SCIENCES  -- Psychology (hsv//eng)

Nyckelord

T cells

CD8

clonality

infection

oldest-old

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)