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Recovery of Delayed-Type Hypersensitivity in Mice Following Suppressive Doses of X-Radiation¹

From the Trudeau Institute Inc., Saranac Lake, N.Y. 12983

Abstract

A study was made of the effects of sub-lethal whole body x-radiation on an established state of delayed hypersensitivity induced by the intravenous infection of mice with M. bovis (BCG) or S. gallinarum. The level of delayed sensitivity was determined by measuring the foot-thickness 24 hr after the injection of a suitable eliciting antigen into the footpad. In appropriately sensitized mice the delayed reactivity to both PPD and the Salmonella antigen was largely suppressed by 400 rad of whole body x-radiation. No recovery of reactivity was detected in the 8 days following irradiation of tuberculin sensitive mice. On the other hand, in mice sensitized to S. gallinarum there was a gradual recovery in footpad reactivity.

X-radiation resulted in an abrupt decline in the absolute numbers of circulating lymphocytes, monocytes but not granulocytes. Low white cell counts were sustained throughout the remainder of the experiment. Concurrent autoradiographic labeling studies showed a fall in the labeling index of mononuclear exudate cells at the reaction site coincident with minimal footpad reactivity. The subsequent return of a normal labeling index in the cells of the infiltrate was associated with the recovery of a significant degree of specific footpad reactivity. These results were interpreted to favor the concept that delayed hypersensitivity is mediated by two cell populations. The first is relatively radioresistant and endowed with the specific sensitivity necessary to initiate a delayed reaction. The second, which is necessary for its ultimate expression, is derived from radiosensitive precursors that are capable of rapid regeneration.

Footnotes

This work was supported by Grants AM-11038 and AI-07809 from the National Institutes of Health, United States Public Health Service.