Protection of lethally irradiated mice by spleen cells from neonatally thymectomized mice

Abstract

Long-lived, immunologically vigorous (C3H(f) x A(f))F(1) hybrids were produced after lethal irradiation by administration of spleen cells from C3H(f) or syngeneic donors. Further, neonatally thymectomized C3H(f) or A(f) strain donors reconstituted irradiated C3H(f) or (C3H(f) x A(f))F(1) hosts. In addition, C3H(f) spleen cells from nonthymectomized 10- to 15-day-old donors protected irradiated hybrid mice, but A(f) cells of young mice as well as of older mice produced graft-versus-host reaction and early death in irradiated C3H(f) or (C3H(f) x A(f))F(1) hybrids. Abrogation of secondary disease by treatment of irradiated mice with spleen cells from allogeneic neonatally thymectomized mice is possibly attributable to diminished immunologic competence of the cells grafted, followed by the development of immunological tolerance of the donor cells. Donor cells, receiving thymus influence in the recipient host after transplantation, could explain the long-lived immunologically vigorous radiation chimeras that did not experience graft-versus-host reactions. The findings of this study help to understand the differential susceptibility of A(f) and C3H(f) mice to development of tolerance to one another's antigens observed in prior investigations. It appears that, in these mice, the host thymus influences the maturation of the spleen cells from young mice or from neonatally thymectomized mice. However, this influence was often greater in mice given 767 rads than in those given 1046 rads. This differential influence is possibly attributable to irradiation damage to the thymus produced by the higher dose of irradiation. Spleen cells from neonatally thymectomized mice can be differentiated and expanded by the thymus of the host. The differential susceptibility of T(1), early differentiation stages, of thymus-dependent lymphocytes and T(2), late differentiation stages, of thymus-dependent lymphocytes to tolerance induction and immunostimulation, respectively, are proposed as the bases for these otherwise paradoxical influences.