Rapid turnover of effector-memory CD4(+) T cells in healthy humans

Derek C Macallan, Diana Wallace, Yan Zhang, Catherine De Lara, Andrew T Worth, Hala Ghattas, George E Griffin, Peter C L Beverley, David F Tough, Derek C Macallan, Diana Wallace, Yan Zhang, Catherine De Lara, Andrew T Worth, Hala Ghattas, George E Griffin, Peter C L Beverley, David F Tough

Abstract

Memory T cells can be divided into central-memory (T(CM)) and effector-memory (T(EM)) cells, which differ in their functional properties. Although both subpopulations can persist long term, it is not known whether they are maintained by similar mechanisms. We used in vivo labeling with deuterated glucose to measure the turnover of CD4(+) T cells in healthy humans. The CD45R0(+)CCR7(-) T(EM) subpopulation was shown to have a rapid proliferation rate of 4.7% per day compared with 1.5% per day for CD45R0(+)CCR7(+) T(CM) cells; these values are equivalent to average intermitotic (doubling) times of 15 and 48 d, respectively. In contrast, the CD45RA(+)CCR7(+) naive CD4(+) T cell population was found to be much longer lived, being labeled at a rate of only 0.2% per day (corresponding to an intermitotic time of approximately 1 yr). These data indicate that human CD4(+) T(EM) cells constitute a short-lived cell population that requires continuous replenishment in vivo.

Figures

Figure 1.
Figure 1.
Kinetics of labeling of naive, TCM, TEM, and RA+7− CD4+ T cells after infusion of 2H-glucose. Subjects were infused with 2H-glucose for 24 h starting from time 0, and the proportion of labeled cells (relative to total cells in each subpopulation) at different time points is shown for CD45RA+ (left) and CD45R0+ CD4+ T cells (right). Data for CCR7+ and CCR7− cells are indicated by filled or open symbols, respectively; error bars represent the SD of triplicate GCMS measurements. Lines represent best-fit curves calculated based on the data points and assuming maximal labeling at 24 h.

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