A Quantitative Study of Cellular Immunity

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Abstract
Summary: Mice were injected subcutaneously with either foreign or native strain thymus cells labeled with P32, and the radioactivity of DNA, extracted from the draining nodes and spleen, was determined at days 1 and 2. Intense activity was already present in the nodes and a lesser (although considerable) level of activity was present in the spleens at day 1. This is taken to mean that in mice immunized with thymus, large amounts of antigen reach the lymphoid organs within 24 hr. In mice thus immunized, and in mice immunized with implanted embryo, the fluctuations with time of the cellular immunity of draining nodes and spleens, and in some cases of contralateral nodes or of pooled nodes and of thymus, were measured. The measure used was the assay of Winn, in which serial dilutions of presumptively immune cells are mixed with target tumor cells and implanted subcutaneously in appropriate hosts. Weight of the tumors at 1 week measures the level of immunity. In mice immunized with thymus, a rapid rise to peak immunity was found on days 5 or 6, followed by a rapid decline. The rise in the draining nodes preceded the rise in contralateral nodes and spleen by about 1 day. Immunity persisted at a low level to day 31 when observations were terminated. There was a suggestion of a low point in immunity about days 14 to 17 with a slight rise about day 24. The height of the peak at 5 to 6 days indicated a tremendous production of immune cells. There was measurable immunity in the thymus on day 6, although much less than in the other organs assayed. In mice immunized with embryo, a high level of cellular immunity was also attained, but the immune level dropped less rapidly, and the lag in the spleen as compared with the draining nodes was greater in these mice than in mice immunized with thymus. The cell yield of the draining nodes showed a 2- or 3-fold increase at the time of peak immunity, and fell again as the immunity fell. There was no comparable increase in the spleen, although the immunity per cell was essentially the same in the two organs. The timing of the immune response found in this study is compared with the timing found in histologic studies of the lymphoid organs and with the time relationships of the homograft reaction. An adequate antigenic stimulus sets in motion an abundant production of lymphocytes in the lymph nodes and spleen. Mitoses begin at about 2 days; mature lymphocytes are present at about 6 days and are probably rapidly released. This is concordant with the peak in cellular immunity which we find at days 5 and 6. Also concordant are descriptions of the homograft reaction which show a massive invasion of tumor transplants by lymphocytes or histiocytes (which we presume to be derived from lymphocytes) on approximately day 6. The graft, which flourishes up to this point, at once begins to show degenerative changes. All these facts emphasize the role of the lymphocyte as a specifically immune cell. The possible significance of the immune cell in disease is briefly discussed.

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