Induction of leukemia regression in mice by immunotherapeutic transfer of T-lymphocytes.
The erythroleukemia induced in susceptible mice by Friend virus (FV) is a progressive, lethal disease. A variant strain of Friend virus (regressing FV) produces a histopathologically identical leukemia except that the disease spontaneously regresses in 50% of leukemic mice. Normal T-cell and macrophage function are required for regression to occur and in animals that are going to regress, specifically reactive T-cells are found in the spleen. Passive transfer of sensitized T-cells from regressing FV immunized or regressed mice caused regression of the conventional lethal leukemia induced by FV. To expand the effector cell populations, characterize them and improve their therapeutic efficacy, sensitized T-cells were cultured in vitro. The T-cells, isolated from regressed or immunized mice, were grown and expanded in vitro with interleukin 2 and antigen (mitomycin C treated regressing FV-infected cell lines). The T-cells demonstrated high levels of in vitro cytotoxicity against FV antigens but exhibited no blastogenic response to the same antigens. When fully FV-induced leukemic mice (14 days post virus inoculation; spleen weight, greater than 0.75 g) were given one injection of 5 X 10(6) in vitro cultured T-cells and no other treatment the mice experienced permanent regressions of their disease. From T-cell cultures depleted of specific cell populations with monoclonal antisera, helper Lyt-1+ cells were shown to be responsible for permanent regressions (cures), whereas cytotoxic Lyt-2+ cells caused temporary leukemia remissions. This model thus provides an experimental system of highly effective passive cellular immunotherapy against an autochthonous, fully developed leukemia, requiring no adjunctive treatment for activity.
Johnson
C S
CS
Thurlow
S M
SM
Furmanski
P
P
D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D001853:Bone Marrow / Q000382:microbiology; D005622:Friend murine leukemia virus; D007116:Immunization, Passive; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000628:therapy*; D007942:Leukemia, Experimental / Q000628:therapy*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation
D000950:Antigens, Ly; D007376:Interleukin-2; D007371:Interferon-gamma