Turnover Rate of Normal Blood Lymphocytes and Exchangeable Pool Size in Man, Calculated From Analysis of Chromosomal Aberrations Sustained During Extracorporeal Irradiation of the Blood

Lymphocyte kinetics have been studied in four patients treated by extracorporeal irradiation of the blood (ECIB) for immunosuppressive purposes prior to renal transplantation. The technique involves the analysis of chromosomal aberrations sustained by lymphocytes during irradiation and demonstrable in cultures stimulated with phytohaemagglutinin (PHA). Lymphocytes containing aberrations may be regarded as labeled, and this form of labeling has the advantage that it does not require the manipulation of lymphocytes outside the body. Preliminary experiments established that about half of lymphocytes irradiated with doses of 300-400 rad fail to undergo mitosis in culture and that the aberration yield per lymphocyte is the same at the end of a course of ECIB as at the beginning. Irradiated lymphocytes were found to have a mean residence time in the blood of less than 2 min, and for the first few hours of irradiation they were replaced by lymphocytes from tissue pools at a rate such that there was no appreciable fall in the peripheral count. These findings imply that a large proportion of the vascular endothelium acts as a filter for damaged lymphocytes and that initially damaged cells were replaced at the rate of one blood pool per hour; this may represent the normal turnover time of blood lymphocytes. The size of the total exchangeable lymphocyte pool was calculated by two methods depending on a series of basic assumptions concerning the kinetics of irradiated cells. According to the most likely estimate, the total pool contains some 30 times as many cells as circulate in the blood. Fortytwo per cent of lymphocytes survived an irradiation dose of 300 rad, 10%19% survived 380 rad.