Reassessment of Human Peripheral T-lymphocyte Lifespan Deduced from Cytogenetic and Cytotoxic Effects of Radiation

Abstract

Estimates of the mean lifetime of human peripheral blood T-lymphocytes (PBTL) have ranged from 1·5 to 10 year. To derive an improved estimate, kinetic and dose parameters of four deterministic, two-compartment models of loss and replacement of human peripheral blood lymphocytes (PBL) were fitted to a previously published extensive data set on loss of dicentrics plus rings (DR) in PBL sampled from X-ray-treated ankylosing spondylitis patients for > 20-year-post-treatment, involving a fixed external-dose regimen (with dose to PBL unknown). The four models investigated all incorporated fixed dose–response submodels for radiation-induced cytogenetic damage and cell killing that were based entirely on in vitro data for X-ray-exposed human PBTL. Two of the models are shown to provide a reasonably good prediction not only of the data on DR loss to which the models were fit, but also of corresponding data on recovery of the mean of measured total PBL. The modelling results indicate that it is unlikely that long-lived human recirculating ‘memory’ PBTL are homogeneous with respect to lifespan, but rather that two major subpopulations, T₁ and T₂, are involved having mean lifespans (and ∼ 95% confidence limits) estimated to be ∼ 1·1 (0·76–1·9) and ∼ 6·3 (5·8–6·9) year, respectively. One of the two models consistent with the data posits that T₁ (possibly ‘short-term antigen-memory’) cells are ∼ 60% of recirculating T-lymphocytes that convert at a rate of ∼ 9% year⁻¹ into T₂ (possibly ‘long-term antigen-memory’) cells, and that the T₁ cells are virtually all derived from a central-body source such as thymus and/or central lymphatic tissues.