The role of T cells in allografted tumor rejection: IFN-gamma released from T cells is essential for induction of effector macrophages in the rejection site.
Allografted Meth A tumor rejection is T cell dependent, but T cells are inactive toward the allograft; rather, the main effector cells are allograft-induced macrophages (AIM) with MHC haplotype specificity. Here, we examined the role of T cells in the induction of AIM in the rejection site. On day 4.5 after i.p. transplantation of Meth A fibrosarcoma cells to C57BL/6 (B6) mice, we obtained a kind of precursor of AIM (pro-AIM) from the transplantation site by an enrichment technique involving adherence to serum-coated dishes. The noncytotoxic pro-AIM-rich population put into a diffusion chamber became cytotoxic against Meth A cells after 2 days in the peritoneal cavity of an untreated B6 mouse. Similar activation of the chambered B6 pro-AIM-rich population occurred in IFN-gamma -/- B6 mice, whereas there was no activation when chambers containing an IFN-gamma -/- mouse-derived pro-AIM-rich population were placed in normal or IFN-gamma -/- mice, suggesting that IFN-gamma is involved in the activation. RT-PCR experiments demonstrated that among bulk infiltrates T cells were the major producer of IFN-gamma; and most of the cells in a T cell-eliminated pro-AIM population in a diffusion chamber kept for 2 days in a B6 mouse did not become AIM. Furthermore, IFN-gamma -/- B6 mice could not reject allografted Meth A tumor cells, whereas the grafts were rejected by i.p. injections of IFN-gamma into the mutant mice. These results indicate that IFN-gamma released from allograft-induced T cells is essential for both the activation of a kind of pro-AIM to AIM in the transplantation site and the rejection of an allografted tumor.
Yoneda
Y
Y
Department of Cell Biology, Osaka Bioscience Institute, Suita, Japan.
Yoshida
R
R
D000818:Animals; D005354:Fibrosarcoma / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation / Q000276:immunology*; D012513:Sarcoma, Experimental / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D007371:Interferon-gamma