The role of adoptivley transferred CD8 T cells and host cells in the control of the groth of the EG7 thymoma:factors that determine therelative effectiveness and homing properties of Tc1 and Tc2 effectors

摘要

We had previously examined the factors that regulate the response of OVA-specific TCR-transgenic CD8 T cells to the B16 OVA melanoma, growing as lung metastases. We examine here whether the same parameters operate for EG7, growing intradermally. Tcl or Tc2 CD8 effector cells from OT-1 mice were injected either mixed with the tumor or i.v. at day 0 or 7. Tc2 were one-fifth to one-tenth as effective as Tcl when injected with the tumor, in controlling tumor growth, but were only 1/20 to 1/100 injected i.v. Tcl injected i.v. entered the draining lymph nodes faster than Tc2 and caused a faster accumulation of host cells. Both caused an abrupt termination of host cell entry into lymph nodes and spleen after tumor elimination, but this occurred earlier for Tcl than for Tc2. Host responses were ineffective in the absence of adoptive transfer but were essential after transfer. Perform expression in the donor cells plays no role in adoptively transferred Tcl or Tc2 control of the tumor, and neither IL-4 nor 1L5 is needed for Tcl or Tc2 function. Tcl cells from mice lacking IFN-’y, however, control tumor growth less well, whereas Tc2 effectors lacking IFN-’y are unaffected. Tcl from IFN-y-deficient mice attract fewer host cells to the draining lymph node, whereas Tcl cells from perform-deficient donors are unimpaired. We conclude that host cell recruitment is a crucial element in adoptive immunotherapy. The differences between the EG7 and the previous B16 melanoma model are discussed.