The rate of the CD8-dependent initial reduction in tumor volume is not limited by contact-dependent perforin, Fas ligand, or TNF-mediated cytolysis

被引:36
作者
Hollenbaugh, JA
Reome, J
Dobrzanski, M
Dutton, RW
机构
[1] Trudeau Inst Inc, Saranac Lake, NY 12983 USA
[2] Univ Vermont, Cell & Mol Biol Program, Burlington, VT 05405 USA
关键词
D O I
10.4049/jimmunol.173.3.1738
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Established EG7 tumors expressing OVA and growing at an intradermal site become rapidly reduced in size following adoptive therapy with in vitro-generated type I CD8 T cell (Tc1) effectors generated from naive CD8 T cells from transgenic TCR OVA-specific mice. Tc1 effectors kill EG7 target cells in vitro by a perforin-dependent mechanism. However, we show that there is no quantitative diminution of the initial phase of antitumor activity in vivo, whether the Tc1 effectors are derived from perforin-, Fas ligand-, or TNF-deficient transgenic TCR mice or whether the recipients are perforin deficient. Tumors are also equally well controlled whether the Tc1 effectors come from mice deficient in perforin plus Fas ligand or perforin plus TNF. Control of tumor growth is diminished when Tc1 effectors generated from IFN-gamma-deficient mice are used. We conclude that control of tumor growth is not in any way affected by loss of contact-mediated lytic mechanisms, and conclude that the CD8 effectors must act by recruiting host effector mechanisms to control tumor growth.
引用
收藏
页码:1738 / 1743
页数:6
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