Abstract

Here we report that the slow-transforming helper component of Friend murine leukaemia virus (Fr-MLV), which produces lymphoid leukaemias in normal mice, induces erythroleukaemia in mice given syngeneic pituitary grafts (SPG). Newborn mice were infected with Fr-MLV and, at one month of age, were transplanted with two pituitary glands under the kidney capsule. Sham-operated infected mice and uninfected transplanted mice served as controls. SPG selectively reduced the mean survival times of infected mice. Histopathology showed that, while most infected non-transplanted mice developed lymphoid leukaemias, virtually all Fr-MLF-infected mice given SPG developed erythroleukaemias. Experiments in vitro showed that Fr-MLV infection markedly depressed concanavalin A induced DNA synthesis in cells from spleen, thymus and lymph nodes. Addition of prolactin or growth hormone further suppressed lectin-induced mitogenesis of lymphoid cells from infected mice, but failed to influence the response of uninfected controls. These experiments indicate that, in mice, pituitary hormones modulate the development and the histological features of Fr-MLV induced leukaemias, and suggest that endocrine-immunological interactions play a role in retrovirus induced tumorigenesis.

Highlights

  • Friend murine leukaemia virus (Fr-MLV) was propagated in vivo in adult BALB/c mice and checked free of contamination by both spleen focus forming component of FLV (SFFV) and the lactic dehyrogenase virus

  • All Fr-MLV infected mice receiving pituitary transplants were dead by 300 days of age, while only 35% of mice of the control group were dead by the same time

  • This study indicates that ectopic pituitary transplantation favours the development of Fr-MLV induced leukaemias and switches their histotype from predominantly lymphoid to erythroid

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Summary

Methods

AnimalsInbred virgin female Balb/c mice bred and maintained in our mouse colony were used throughout. Fr-MLV was propagated in vivo in adult BALB/c mice and checked free of contamination by both SFFV (absence of marked and rapidly progressing splenomegaly in adult mice, no development of erythroleukaemia) and the lactic dehyrogenase virus (infected mice have normal LDH levels). Virus preparation consisted of filtered plasma with a titer of 3 x I05 PFU ml-' as tested on monolayers of murine FG 10 (S+L-) cells (Toniolo et al, 1984). This strain has been extensively used in previous work and is immunosuppressive in adult as well as in newborn mice (Bendinelli et al, 1985). The induction of erythroleukaemia by Fr-MLV depends on the age of animals at the time of infection. Mice older than 2-3 days never develop erythroleukaemia; the disease occurs when mice are infected within 24 h from birth (unpublished observations in agreement with those of Oliff et al, 1981; Ruscetti et al, 1981; Shibuya & Mak, 1982)

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