In vivo estimates of division and death rates of human T lymphocytes.

Abstract

We present data on the decay, after radiotherapy, of naive and memory human T lymphocytes with stable chromosome damage. These data are analyzed in conjunction with existing data on the decay of naive and memory T lymphocytes with unstable chromosome damage and older data on unsorted lymphocytes. The We use two data sets from which to estimate life-history parameters of human T lymphocytes in vivo. Both come from cross-sectional studies of the number of lymphocytes with radiation-induced chromosomal damage. The data of Buckton et at (6) record the proportion of lymphocytes with stable and unstable damage in men given radiation therapy as treatment for ankylosing spondylitis. The data of Michie (7) record the proportion of T lymphocytes of primed and unprimed subsets with stable and unstable damage. By using these two data sets, we are able to estimate death rates, proliferation rates, and interconversion rates for primed and unprimed T lymphocytes. We then use these rate estimates as parameters for a simple mathematical model of the population dynamics of peripheral T cells. Investigation of the behavior of this simple model allows us to make some inferences about the broader implications of the data. METHODSBuckton's Data. Full details concerning the methods for collecting these data are given in the original paper (6). We give a brief summary. One hundred and twenty-nine venous blood samples were taken from 66 men between 0 and 3700 days after they had received x-ray treatment for ankylosing spondylitis. Chromosome preparations were made from lymphocytes and classified into groups by the method of Buckton and Pike (4). Data were then aggregated into 14 groups of 8-12 observations. Only the aggregated data were reported and it is these aggregated data that we use. Although Buckton's samples must have contained small numbers of B cells, we assume that they are present in such small proportions that we can ignore them. We therefore treat Buckton's data (6)

Measurement and modeling of human T cell kinetics

“…This study confirms that such 'memory' cells have a faster rate of turnover than 'naive' cells, as previously described in human in vivo labeling studies [4], in murine studies using BrdU [1], and in human studies based on disappearance of radiationinduced chromosomal damage, where turnover rates in CD45RO + cells were eight-times those in CD45RA + cells [2]. However, the absolute rates found using chromo-somal analysis were considerably slower than the rates found here; this disparity might arise from differences in the population of cells studied, exclusion of early celldeath events in the radiation studies or pathological effects on irradiated cells.…”

“…Bromodeoxyuridine (BrdU) labeling in murine and ovine studies has contributed enormously to our understanding of T cell homeostasis [1]. In humans, disappearance rates of cells bearing chromosomal damage induced by diagnostic or therapeutic irradiation have confirmed heterogeneity within T cell pools; CD45RO + cells disappear more rapidly than their CD45RA + counterparts [2]. More recently, stable (non-radioactive) tracer studies have directly measured T cell proliferation rates in vivo in healthy individuals and in HIV infection, initial studies yielding proliferation rates of about 0.9% and 0.5% / day for CD4 and CD8 cells, respectively, in healthy subjects [3,4].…”

An IFN-γ-Dependent Pathway Controls Stimulation of Memory Phenotype CD8+ T Cell Turnover In Vivo by IL-12, IL-18, and IFN-γ

“…This was also shown to apply to memory T cells of known antigenic specificity using TCR-transgenic mice (7,8). The rapid turnover of memory T cells contrasts with that of naive T cells, which rarely, if ever, divide in the absence of overt stimulation by specific Ag (3,4,9,10). The implication is that the memory T cell pool is maintained at least in part by periodic cell division, raising the important question of what factors are driving the cell turnover.…”

T-cell reconstitution and expansion after hematopoietic stem cell transplantation: ‘T’ it up!

“…47 In HIV-1 infected adults on antiretroviral therapy, deuterated glucose measurements indicate that the half-lives of naive-phenotype T cells ranges from 116 to more than 365 days, whereas T cells of the memory/effector-phenotype persisted with half-lives from 22 to 79 days. 48 T cells are different from most other tissues such as in the case of red blood cells where survival is related to lifespan of the cells and the oldest cells are removed first.…”