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Interferon-induced Inhibition of Moloney Sarcoma Virus-transformed Cells: Requirement for T-Cells¹

Department of Microbiology and Immunology [M. B. S-M, S. N. M., D. M. M.] and Department of Surgery [M. B. S-M.], The Medical College of Pennsylvania, Philadelphia, Pennsylvania 19129

We previously demonstrated that although natural killer (NK) cells participated in interferon (IFN)-induced inhibition of growth of the Moloney sarcoma MSC cell tumor, the need for NK cells could be circumvented by using a small tumor cell challenge or an increased amount of IFN. These studies were performed in normal, euthymic mice. The role of T-cells remained undefined. In the present study, nude mice were used to evaluate the role of T-cells. Investigation of various treatment regimens revealed that IFN could not totally inhibit tumor growth in nude mice. A significant delay in tumor growth was observed when 1 x 10⁵ units of IFN were administered at the site of tumor on days 1–4 after tumor challenge. Increasing the dose of IFN or extending therapy to 7 days did not afford any further inhibition of tumor growth. In vivo depletion of NK cells with anti-asialo monoganglioside antibody revealed that the delay in tumor growth was dependent on NK cells when IFN was given on days 1–4. Treatment for days 1–7, however, still inhibited tumor growth in the NK cell-depleted nude mice. In order to further ascertain the role of T-cells in IFN-induced tumor inhibition, T-cell reconstitution studies of nude mice were performed. Nude mice were reconstituted with 1 x 10⁷, 2 x 10⁷, and 5 x 10⁷ T-cells on day -1 to tumor challenge and treated with IFN on days 1–7. The extent of the observed decrease of tumor sizes and tumor incidences among the T-cell-reconstituted groups was dependent on the dose of T-cells being administered in both IFN-treated and untreated animals.

These data indicate that T-cells are essential for maintaining the growth-inhibitory effects of IFN. This is in contrast to NK cells whose role in IFN-induced inhibition of MSC tumor growth can be circumvented by increasing the dose of IFN.

¹ This work was supported by NIH Grant CA43386.

² To whom requests for reprints should be addressed, at Department of Microbiology and Immunology, The Medical College of Pennsylvania, 3300 Henry Ave., Philadelphia, PA 19129.

Received 7/11/88. Revised 10/ 3/88. Accepted 10/21/88.