Quantitative studies on tissue transplantation immunity VIII. The effects of irradiation

Abstract

This paper describes and attempts to interpret the effects of X- and gamma-irradiation on transplantation immunity. Whole-body irradiation prolongs the life ofA-strain skin homografts onCBAmice. Over the range 0 to 600 r the reciprocal of their survival time (x) is simply proportional to the applied radiation dosage (y), so that 1/x= 1/a–ky, wherearepresents the survival time of the homografts on unirradiated mice, andkis a constant of proportionality. At all doses skin homografts lasted significantly longer on males than on females, behaviour attributed to a higher intrinsic immunological reactivity of females rather than to a higher radioresistance. The normal lymphocyte transfer (NLT) reaction—an immunological response of the graft-versus-host type aroused by injecting lymphoid cells from one guinea-pig into the skin of another—has been made the basis of a more detailed investigation of how irradiation affects transplantation immunity. Lymphoid cells were exposed to a60Co radiation source eitherin vitro, i.e. in transit between donor and recipient, or in the donor before cell transfer, or in the recipient after cell transfer. As an entirely separate consideration, all lymphocyte recipients were exposed to 600 r whole-body irradiation before transfer to allow the NLT reaction to run a full course without the immunological opposition which the lymphocytes would otherwise arouse as homografts. Applied to transferred lymphocytesin vitroorin vivo, radiation dosages up to at least 1000 r did not affect the first inflammatory episode of the NLT reaction, i.e. the specific immunological event thought to mark the first recognition of antigen (see the preceding paper); nor did it affect the immediate immunological performance of lymphoid cells which had been presensitized against the guinea-pigs into which they were injected. The effect of radiation was only to suppress (at lower doses) or to abolish (at higher doses) the ‘flare-up’ episode of the NLT reaction, i.e. the conversion of a normal into a sensitized population, presumably as a result of cell division. It is accordingly argued that irradiation affects no distinctively immunological performance of lymphoid cells, and that the effects of irradiation can be explained by (a) its antiproliferative action, and (b) the fact that lymphocytes, though abnormally radiosensitive, acquire a relatively high degree of radioresistance as soon as exposure to antigen commits them to an immunological response. Members of a lymphoid population which have survived exposure to 600 r whole-body irradiationini vivo24 h beforehand perform more strongly than normal lymphoid cells in the NLT reaction. Internal evidence does not make it possible to decide between several possible interpretations of this fact.