The role of adoptively transferred CD8 T cells and host cells in the control of the growth of the EG7 thymoma: Factors that determine the relative effectiveness and homing properties of Tc1 and Tc2 effectors

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. Tel or Tc2 CD8 effector cells from OT-1 mice were injected either mixed with the tumor or Lv. at day 0 or 7. Tc2 were one-fifth to one-tenth as effective as Tel when injected with the tumor, in controlling tumor growth, but were only 1/20 to 1/100 injected Lv. Tel 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 Tel than for Tc2. Host responses were ineffective in the absence of adoptive transfer but were essential after transfer. Perforin expression in the donor cells plays no role in adoptively transferred Tel or Tc2 control of the tumor, and neither IL-4 nor IL5 is needed for Tel or Tc2 function. Tel cells from mice lacking IFN-gamma, however, control tumor growth less well, whereas Tc2 effectors lacking IFN-gamma are unaffected. Tel from IFN-gamma -deficient mice attract fewer host cells to the draining lymph node, whereas Tel cells from perforin-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.