Immunosuppression during viral oncogenesis. IV. Generation of soluble virus-induced immunologic suppressor molecules

We describe herein functional attributes and generation of immunologic suppressor activity elaborated in response to oncogenic virus infection. Malignant rabbit fibroma virus-induced immunologic suppressor factor (VISF) is a T cell product produced in peak quantities by spleen cells taken from infected rabbits 7 days after infection in vivo. Its production does not appear to require macrophage participation. VISF is highly labile, 3.5 to 12 kDa, and capable of suppressing both B and T lymphocytic responses. Indomethacin and the cyclic nucleotides cAMP and cGMP inhibit its generation. VISF activity is neither antigen nor species specific. It suppresses murine and leporine immune responses to antigens unrelated to the inducing virus. Comparable suppressor activity may be induced by infecting an apparently non-functional rabbit T lymphoma line, RL-5, with malignant rabbit fibroma virus. VISF is principally a suppressor-inducer factor: in vitro, lymphocytes exposed to VISF do not show decreased immunologic responsiveness until 4 days of culture. VISF induces T suppressor cell activity when normal spleen cells are exposed briefly to VISF. Thus, immunosuppressive consequences of malignant fibroma virus infection are partially mediated by a small, non-specific T cell-derived suppressor lymphokine with unique functional characteristics. Non-specific immunologic dysfunction that often attends virus infections may reflect the activity of such factors in humans as well.