IL-6 secretion by a rat T9 glioma clone induces a neutrophil-dependent antitumor response with resultant cellular, antiglioma immunity.
Previously, we reported that IL-6 transduction attenuates tumor formation of a rat T9 glioma clone (termed T9.F). This study focuses on the mechanisms of the antitumor response elicited by IL-6 and the generation of glioma immunity. Ten days post s.c. inoculation of T9. F- or IL-6-secreting T9.F cells (T9.F/IL6/hi), tumor nodules were removed and their leukocytic infiltrate was analyzed by FACS with Ab markers for T cells, B cells, granulocytes, and monocytes. T9. F/IL6/hi tumors showed a marked increase in granulocytes as compared with parental T9.F tumors, and histological examination revealed that the granulocytes were neutrophils. Animals made neutropenic failed to reject T9.F/IL6/hi tumors. FACS analysis of 17-day T9. F/IL6/hi regressing tumors and T9.F progressing tumors did not reveal any significant differences in the leukocytic infiltrates. Tumor-specific effector cells were detected in the spleens harvested from animals bearing 17-day, regressing, T9.F/IL6/hi tumors. In vitro, these effector cells lysed T9.F cells, proliferated in response to T9.F stimulator cells, and produced Th1 cytokines (IL-2 and IFN-gamma) but not the Th2 cytokine, IL-4, when cocultured with T9.F stimulator cells. Rats that had rejected s.c. T9.F/IL6/hi tumors displayed a delayed-type hypersensitivity response when injected with viable T9.F cells in the contralateral flank. Passive transfer of spleen cells from these animals transferred glioma immunity to naive recipients and depletion of CD3(+) T cells, before transfer, completely abolished immunity, whereas depletion of CD8(+) T cells had moderate inhibitory effects on the transfer of immunity.
Graf
M R
MR
Division of Neurosurgery, Virginia Commonwealth University/Medical College of Virginia, Richmond, VA 23198, USA. mgraf@hsc.vcu.edu
Prins
R M
RM
Merchant
R E
RE
D019264:Adoptive Transfer; D000818:Animals; D002999:Clone Cells; D018920:Coculture Techniques; D005260:Female; D005910:Glioma / Q000276:immunology* / Q000378:metabolism* / Q000517:prevention & control; D006084:Graft Rejection / Q000276:immunology; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007156:Immunologic Memory; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009504:Neutrophils / Q000276:immunology*; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000637:transplantation
D015850:Interleukin-6