Direct measurement of T cell subset kinetics in vivo in elderly men and women

Abstract

The age-associated decline in immunocompetence is paralleled by changes in the proportions of PBL subpopulations. In turn, the size and composition of the peripheral lymphocyte pool is determined by input from the thymus and bone marrow and by the balance of proliferation and death in each lymphocyte subpopulation. We compared the kinetics of lymphocyte subtypes in young (seven of eight CMV seronegative) and healthy elderly human subjects (six of seven CMV seropositive), using deuterated glucose DNA labeling in vivo to measure rates of T cell proliferation and disappearance. For CD45RO+ cells of both CD4+ and CD8+ subtypes and for CD4+CD45RA+ cells the kinetics of proliferation and disappearance were remarkably similar between elderly and young subjects. In the young, the kinetics of CD8+CD45RA+ cells with a naive phenotype resembled those of CD4+CD45RA+ cells. However, CD8+CD45RA+ T cells from the elderly exhibited a predominantly primed phenotype, and for this subset, although the proliferation rate was similar to that of other CD45RA+ cells, the disappearance rate of labeled cells was greatly decreased compared with that of all other T cell subsets. Our data provide a direct demonstration that there are no substantial changes in in vivo kinetics for most T cell populations in healthy elderly compared with young subjects. However, primed CD8+CD45RA+ cells show unusual kinetic properties, indicating the persistence of these cells in the blood and dissociation of proliferation from disappearance.