Development of Runting Syndrome in Friend and Gross Virus-induced Doubly Tolerant Rats¹

Neonatal injections of Friend virus (FV) or Gross virus (GV) into rats produced immunological tolerance to the virus-induced tumors. The inoculation of specific immune lymphoid cells into the FV-induced tolerant rats brought about the runting syndrome, whereas the GV-induced tolerance was completely abrogated by the same procedure. To investigate the mechanism of the runting syndrome, rats were made doubly tolerant by neonatal injections of a mixture of FV and GV. The adoptive transfer of lymphoid cells from rats immunized with the FV-induced lymphomas into the doubly tolerant rats produced the runting syndrome. On the other hand, adoptive transfer of lymphoid cells from rats immunized with GV lymphomas into the doubly tolerant rats did not produce the runting syndrome and broke down the GV-induced tolerance but not the FV-induced tolerance. By the use of a complement-dependent cytotoxicity test, FV-infected cells were homogeneously detected in thymus, spleen, and bone marrow of the doubly tolerant rats, whereas GV-infected cells were detected only in the thymus. Studies with a rosette formation test as a rat thymus marker showed that none of the FV lymphomas formed rosettes with guinea pig erythrocytes, whereas GV lymphomas formed rosettes. These results suggest that FV and GV have different target cells for infection and transformation and that the development of the runting syndrome is closely associated with infection of bone marrow and spleen cells with FV.