Lymphocytic Recovery after Irradiation and its Relation to Other Aspects of Haemopoiesise

Abstract

THE lymphocyte is a very radio-sensitive cell and tissues which contains lymphocytes, whether lymphopoietic or not, are markedly depleted of these cells, after exposure to even small doses of ionizing radiation. A quantitative study of the fall in the lymphocyte content of the bone marrow and blood of the irradiated rat has already been reported (Hulse, 1959a) and the present paper reports on their reappearance in these situations during recovery.One of the current theories of haemopoiesis suggests that the small lymphocyte is a multipotential stem cell (Yoffey, 1960a). The repopulation of bone marrow which has been depleted of cells by radiation is very suitable for testing such an hypothesis. The return of the lymphocytes to the depleted marrow has, therefore, been correlated with the recovery of erythropoiesis and myelopoiesis in the same animals. METHODA full description of the quantitative methods has been given in previous publications (Hulse, 1957(Hulse, , 1959a, the principle behind the marrow examination being the dispersion of a known quantity of femoral marrow in a suitable fluid. Blood examinations were performed on heart blood obtained at the time of killing the animals, immediately prior to extracting the marrow. Details regarding dosage of radiation and the type of rats used in the present investigation have already been given (Hulse, 1961). For each of the three doses used, 100,200 and 400 R., studies were made for 14,42 and 70 days respectively. In the figures (see below), the points relating to irradiated animals are means obtained from three (or in a few instances, four) rats. The data from unirradiated animals represent means from 41 rats, one animal from each litter being used as a control. RESULTSChanges in the blood and bone marrow during the first 48 hours after irradiation are reported first so that the present results may be compared later with those of the previous experiments (Hulse, 1959a). Initial DepletionMarrow lymphocytes. After each of three doses a minimum value was obtained at 2 days after irradiation, the reduction in cell numbers being least after IOO R. and greatest after 400 R. (Fig. I). At 48 hours after 400 R. the marrow lymphocytes were reduced to 13 per cent of normal but as early as 4 hours after irradiation they were reduced by as much as one-third. Thus the rate of depletion was greatest during the first few hours.Blood lymphocytes. These cells were reduced in number more than the marrow lymphocytes but minimum values were again obtained at 2 days ( Fig. I). Of these three doses 400 R. had the 3 76 * Postal address: M.R.C. Radiobiological Research Unit, Harwell, Didcor, Berks. Lymphocytes and Haernopoiesis ajier Irradiation3 77 greatest effect, the blood lymphocytes being reduced to 2.5 per cent or normal at 48 hours.As early as 4 hours after 400 R. they were reduced by two-thirds again indicating that the rate of depletion was greatest during the first few hours. RecoveryMarrow lymphocytes (Fig. I). Definite increases in numbers were seen at 3 days after roo and zoo...

Bone Marrow Lymphocytes of the Rat as Studied by Autoradiography

“…Furthermore, Bierring found that marrow lymphocytes did not decrease in thymectomized rats (4). H ulse has pointed out that bone marrow lymphocytes recover much more quickly following whole body x-irradiation than do peripheral lymphocytes (13). Although the cells may have migrated into the marrow from some other lymphoid area, the findings tend to support the view of O smond and Everett that the marrow lymphocyte population is self-sustaining and has a rapid turnover.…”

“…A number of reports have suggested that the small lymphocytes in the bone marrow of rats and guinea pigs have a different rate of turnover from small lymphocytes in the peripheral lymph nodes and spleen (12,13). These findings have been implemented by the studies of E v e r e t t et al (8, 18) who found a high percentage labeling of bone marrow lymphocytes in normal guinea pigs 24 to 48 hours after a single dose of tritiated thymidine (H3Tdr).…”

Recovery of Haemopoiesis after Cyclophosphamide

“…The present results indicate that the patterns of regeneration are different for each of these cell-lines; they will therefore be considered separately. It is perhaps necessary to add that recovery has only been studied over a period of 21 days and that long term effects such as occur after irradiation [11,12] have not been excluded. Furthermore, the changes in the spleen weight (table IV), and particularly the striking increase in weight at 12 days after cyclo phosphamide, serve to emphasize that the patterns of recovery seen in the bone marrow need to be considered in relation to changes in the rest of the lympho-myeloid complex.…”

“…The latter observation confirmed the findings of H a rris [3,5] in guinea pigs. The rise in marrow lymphocytes has been shown to depend on the dose of irradiation [12]. By means of studies of DNA-synthcsis H arris et al [6] also showed that a consider able proportion of the small lymphocytes in the irradiated marrow were newly formed.…”

Quantitative Cell Counts of the Bone Marrow and Blood and their Secular Variations in the Normal Adult Rat

“…During a quanti tative study of the changes in haemopoiesis after irradiation (17,18,19,20,21,22) a total of 81 noi'mal unirradiated rats were ex amined by a method based on that of Yoffey (36). As comparatively little has been published on values obtained using quantitative methods and as the present series is much larger than those pre viously published, an analysis of the data from the normal rats has been made.…”