MASSIVE MAMMARY-GLAND INFECTION AND PREGNANCY-DEPENDENT MAMMARY-TUMORDEVELOPMENT IN MICE INFECTED NEONATALLY WITH MOUSE MAMMARY-TUMOR VIRUS (SW) BUT NOT IN MICE INFECTED AS ADULTS, DESPITE A DRAMATIC LOCAL RESPONSE

Mouse mammary tumor virus (MMTV) (SW) caused a high incidence (65 %) o f pregnancy-dependent adenocarcinomas in BALB/c(SW) mice infected as n ewborns by suckling their mothers' milli. These tumors were type B ade nocarcinomas which developed early, at about 1 year of age. Uninfected breeding females and those infected at an age of 8 weeks by injection of virus had the same low incidence of malignant tumors (13 %), and t he tumors developed later (at approx. 23-24 months). The low incidence of tumors in adult-infected mice was correlated with partial infectio n of the mammary glands, and delayed transmission of MMTV(SW) to the o ffspring. Although the virus was rapidly disseminated in both types of infection, the responses of neonatally infected and adult-infected mi ce to MMTV(SW) infection and viral superantigen (vSAG) presentation we re different. Activation by and presentation of the vSAG was impaired in mice infected neonatally, and tolerance induction by clonal deletio n was delayed. Local activation was dramatic in mice infected as adult s and clonal deletion followed rapidly. Although interaction between B and T cells is needed for completion of the virus life cycle and vira l amplification, the strong local immune response to MMTV(SW) in adult -infected mice limits mammary gland infection, and protects them again st mammary tumor development.