Effector mechanisms operative in adoptive therapy of tumor-bearing animals: implications for the use of interleukin-2.
Disseminated tumors growing progressively in syngeneic hosts can be eradicated by combination therapy with cyclophosphamide and adoptive transfer of specifically immune T cells. Interleukin-2 (IL-2), which induces proliferation of T cells specifically activated by antigen, has substantial therapeutic potential as a reagent for increasing the magnitude of tumor-specific T cell responses. The purpose of the present studies was to determine the effector mechanisms operative in tumor-bearing hosts by which subpopulations of immune T cells can mediate tumor eradication, and to determine if the in vivo administration of exogenous IL-2 can augment these T cell effector functions. Disseminated leukemia was eradicated by adoptive therapy with the immune Lyt 1+2- noncytolytic T cell subpopulation, under experimental conditions in which cytolytic T lymphocytes could not participate. The Lyt 1+2- subset contains helper/amplifier cells that produce endogenous IL-2 in response to tumor and effector cells that mediate delayed-type hypersensitivity reactions. The administration of exogenous IL-2 following transfer of immune T cells containing this noncytolytic subset failed to augment their therapeutic activity, implying that the amount of IL-2 being produced endogenously did not limit the antitumor response. Adoptive therapy with purified cytolytic Lyt 1-2+ T cells produced a demonstrable but limited antitumor effect. Since this cytolytic subpopulation lacked helper T cells, the limited activity observed presumably reflected a requirement for an IL-2-producing cell. Administration of exogenous IL-2 following cell transfer satisfied this requirement and markedly augmented the efficacy of adoptive therapy with Lyt 1-2+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D007116:Immunization, Passive; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology*; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D007376:Interleukin-2; D003520:Cyclophosphamide