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We re-appraised the cell renewal pattern in Hodgkin's disease (HD), considering that most, though not all, Hodgkin/Reed-Sternberg (H-RS) cells exhibit abortive mitoses and that a substantial fraction of these exhibits DNA damage suggestive of imminent or actual cell death. Using combined immunohistochemistry and in situ end-labeling to detect strand breaks, the percentage per case of CD30+ (mainly H-RS) cells with DNA fragmentation (DNA fragmentation index [DFI]) was estimated. For each case, we registered the mitotic index (MI) of CD30+ cells and the percentage of Ki-67+ atypical large cells. To quantify the sum of our parameters for mitosis, whether successful or not, and DNA damage, we introduced the kinetic event index (KEI = MI + DFI). Only DFI and KEI distinguished significantly between mixed cellularity and nodular sclerosis HD. The values for MI and DFI, and therefore for KEI, CD30+ and CD30- small lymphoid cells were proportional. The percentages of Ki-67+ large atypical cells (median 50%) did not correlate significantly with either MIs or DFIs of CD30+ cells. Cluster analysis revealed the existence, independent of histological subtype, of 2 large groups of HD with different KEIs. Our findings suggest that cell deletion plays an important role in HD. Further, it appears that proliferation-associated antigens in H-RS cells do not reflect successful cell production in this disorder.

The proliferative activity and rate of cell renewal of, and incorporation of tritiated nucleosides into, macrophages, reticuloendothelial cells and fibroblasts were studied in lymph nodes of mice before and after a regional second antigenic stimulus with tetanus toxoid. Histological and autoradiographic examinations revealed that in non-stimulated nodes of animals primed 6 months previously, none of the above cell-types was found to synthesize DNA. Throughout a period of 10 days following secondary antigenic stimulation via the hind leg foot pads, only four of approximately five thousand of these cells counted in the popliteal lymph nodes of thirty-four mice were labelled initially by [3H]thymidine. Incorporation of [3H]cytidine could, therefore, be interpreted as reflecting almost exclusively RNA synthesis. Mean grain counts of non-proliferating cells 1 hour after injection of this radioactive precursor started to rise first in small lymphocytes, reached a peak around 6 hours following the booster injection of antigen and returned to slightly elevated values at 12 hours. At this time, the mean labelling intensity of macrophages, reticuloendothelial cells and fibroblasts had barely begun to increase. Peak values for the latter cell-types were attained only on the third day after secondary antigenic stimulation. These findings are interpreted as indicating consecutive waves of enhanced RNA synthesis first in lymphocytes and then in macrophages or the other elements mentioned above. This lends further support to the hypothesis that, following a second injection of tetanus toxoid, elevated rates of RNA synthesis in macrophages are not a prerequisite for triggering lymphocytes to enter proliferation and differentiation. Macrophages having ingested various materials showed significantly higher mean grain counts than cells not containing cytoplasmic inclusions. One early response of the macrophage system to the booster injection of antigen consisted of a more rapid and increased turnover, i.e. replacement of unlabelled by labelled cells with increasing time after injection of [3H]thymidine. The results are discussed in relation to macrophage functions in immune responses and possible cellular transformations in the macrophage series.

Juvenile Swiss mice experienced significant diminutions in thymic content of both small, non-proliferating and larger, proliferating lymphocytes within 12 hours after intraperitoneal injection of phytohaemagglutinin. These alterations, which may predate alterations in lymphocyte traffic and morphology elsewhere, were interpreted as being the consequence of a massive thymus lymphocyte emigration, not of in situ cytolysis, and were effaced by intrathymic lymphocyte restoration toward control numbers by 24 hours.