Delayed tumour appearance and absence of regression in nude mice infected with murine sarcoma virus.
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Biomedical subjects
Publications and source records attributed to O Stutman.
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Tryptic peptide maps were prepared for four purified structural proteins derived from several murine leukemia viruses (MuLV's). Analyses of these peptide maps reveal that the p30 proteins of Rauscher, Moloney, and Gross MuLV's are very similar to each other, as are the p10's obtained from these three viruses. In contrast, the peptide maps of the individual p15's and p12's from the same viruses establish that each of these polypeptides is highly strain specific. For all four polypeptides studied, unique peptides appear in the Rauscher MuLV and Moloney MuLV tryptic profiles that are not present in the corresponding Gross MuLV profile. By this method of analysis it was possible to distinguish the p30's of N-tropic and B-tropic MuLV's derived from the same BALB/c mouse.
The murine fetal thymus obtained early in gestation was found to develop normally in a syngeneic host. In contrast to the adult thymus grafts, the fetal thymus did not undergo the early and marked necrosis following transplantation into syngeneic hosts. Indeed, the fetal thymus was as effective as the adult thymus in achieving immunologic reconstitution of neonatally thymectomized syngeneic mice, and superior to adult thymus, when transplanted into allogeneic hosts. Furthermore, the fetal thymus, unlike the adult thymus, did not induce graft-vs-host disease (GVH) in genetically susceptible neonatally thymectomized mice. These observations seem relevant to thymus transplantation in children with a congenital absence of the thymus. Transplantation of fetal thymus in a child with DiGeorge syndrome corrected the T-cell immunodeficiency, and led to a reduction toward normal of the B-cell population.
Athymic-nude (nu/nu) mice and normal (nu/+) mice showed no differences in either latent period or incidence of local sarcomas or lung adenomas within 120 days after administration of 3-methylcholanthrene at birth. However, nu/nu mice were incapable of rejecting allogeneic skin grafts for the duration of the experiment. These results argue against an active role of thymus-dependent immunity as a surveillance mechanism preventing tumor development.
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.
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