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
Bk. Helmich et Rw. Dutton, 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, J IMMUNOL, 166(11), 2001, pp. 6500-6508
We had previously examined the factors that regulate the response of OVA-sp
ecific TCR-transgenic CD8 T cells to the B16 OVA melanoma, growing as lung
metastases. We examine here whether the same parameters operate for EG7, gr
owing intradermally. Tel or Tc2 CD8 effector cells from OT-1 mice were inje
cted either mixed with the tumor or Lv. at day 0 or 7. Tc2 were one-fifth t
o one-tenth as effective as Tel when injected with the tumor, in controllin
g 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 accumu
lation of host cells. Both caused an abrupt termination of host cell entry
into lymph nodes and spleen after tumor elimination, but this occurred earl
ier for Tel than for Tc2. Host responses were ineffective in the absence of
adoptive transfer but were essential after transfer. Perforin expression i
n the donor cells plays no role in adoptively transferred Tel or Tc2 contro
l 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 conclud
e that host cell recruitment is a crucial element in adoptive immunotherapy
. The differences between the EG7 and the previous B16 melanoma model are d
iscussed.