Friend virus replication in normal and immunosuppressed C57BL/6 mice.

Young adult C57BL/6 mice are resistant to the replication of Friend virus. We show here that this resistance is not absolute. In 7-week old C57BL/6 mice injected with NB-tropic Friend virus iv, high titers of SFFV could be recovered from the spleen at 8 days after infection but by 21 days, no virus was detectable. A single dose of anti-Thy 1.2 monoclonal antibody iv before FV infection permitted continued replication of SFFV in these animals. This finding strongly supports the hypothesis that SFFV replication in C57BL/6 mice is restricted by a T cell-mediated immune response.

Immunosuppression after injection of Friend virus into C57BL/6 mice of different ages.

Injection with Friend virus (FV) causes immunosuppression in young and old C57BL/6 mice, i.e. it occurs whether or not the virus replicates very briefly or for a long period. There are only minor age-related differences in the extent of immunosuppression, except that suppression appears to persist somewhat longer in old than in young animals.

Friend virus replication as a function of age.

We have investigated the effect of age on the replication of Friend spleen focus-forming virus (SFFV). Recovery of SFFV from the spleens of four strains of mice was determined following intravenous infection with NB-tropic Friend virus (FV) complex at ages ranging from 6 to 134 weeks. In C57BL/6 mice, the virus did not replicate in adults up to 40 weeks of age, but beyond that there was a steep exponential increase with age in the amounts of SFFV recoverable. In C3H/He mice, which replicate the virus as young adults, the amount of SFFV recovered was 6-fold greater in old than in young mice. Recovery of virus was biphasic with age in SJL mice; in A strain mice no consistent change with age was noted. In C57BL/6 mice, reconstitution of lethally irradiated recipients with syngeneic marrow cells, followed by i.v. infection with FV, showed that the amounts of SFFV recovered depended on the age of the recipient. The present work shows that Friend SFFV replication is a sensitive indicator and can be used as a tool for the investigation of aging processes. The mechanisms responsible for the age-dependent change in regulation of virus replication and for the polymorphism remain to be determined.

Tumor colony formation by Friend virus-infected cells in immunosuppressed mice.

We have investigated the role of host immunological factors in the formation of "tumor colonies" in the spleens of unirradiated C57BL/6 X C3Hf/Bi FI mice 9 days after i.v. injection of spleen cells from Friend virus (FV)-infected C3Hf/Bi donors. Pretreatment of hosts with antilymphocyte serum (ATS) increased the number of tumor colonies. Pretreatment with formalinized FV-infected cells had the opposite effect, and ATS diminished the inhibitory effect of preimmunization. Cell suspensions from 11 individual FV-infected donors were examined. The suspensions differed with respect to their behavior on transplantation into untreated and ATS-pretreated F1 hybrid hosts. With several suspensions, the number of tumor colonies produced was approximately proportional to the number of cells injected; in all of these, ATS increased the slope of the line relating colony number to cell number. With most of the suspensions, tumor colony-forming efficiencies in untreated hosts strikingly decreased with increasing number of cells injected; ATS induced an increase in the number of tumor colonies and rendered the colony-forming response more nearly proportional to cell number. With two suspensions, few or no colonies developed; pretreatment with ATS had no significant effect. When the 11 cell suspensions were considered together, a proportional relation was found between the magnitude of the ATS effect (i.e., colony number in the presence of ATS minus colony number in the absence of ATS) and the colony-forming efficiency in ATS-treated mice. The ATS effect on the average was equivalent to a 2-fold increase in tumor colony-forming efficiency. We interpret these findings to indicate that two factors interact to determine the number of tumor colonies produced by spleen cells from FV-infected C3H donors in untreated F1 hybrid hosts. One is a property of the FV-infected cell population and includes its frequency of tumor colony-forming units; this factor varies widely among different cell suspensions. The other is a property of the tumor colony-forming units-host interrelationship and includes the vulnerability of tumor colony-forming units to the host immune response elicited by the injected cells; this factor appears to be constant with different cell suspensions. The present results show that the two factors can be dissociated in immunosuppressed hosts.