Interferon-induced inhibition of Moloney sarcoma virus-transformed cells: requirement for T-cells.
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 10(5) 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 10(7), 2 x 10(7), and 5 x 10(7) 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.
Skicki-Mullen
M B
MB
Department of Microbiology and Immunology, The Medical College of Pennsylvania, Philadelphia 19129.
Markovic
S N
SN
Murasko
D M
DM
D000818:Animals; D002472:Cell Transformation, Viral; D005260:Female; D007372:Interferons / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008980:Moloney murine sarcoma virus; D012513:Sarcoma, Experimental / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D007372:Interferons