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Trudeau Institute, Saranac Lake, NY 12983
Cytolytic CD8+ T cells fall into two subpopulations
based on cytokine-secretion. Type 1 CD8+ cells (Tc1)
characteristically secrete IFN-
, whereas type 2 CD8+
cells (Tc2) secrete IL-4 and IL-5. We assessed the relative therapeutic
effects of adoptively transferred OVA-specific Tc1 and Tc2
CD8+ cells in mice bearing established OVA-transfected B16
melanoma lung metastases. Both Tc1 and Tc2 subpopulations mediated a
reduction in lung tumor growth that subsequently prolonged survival
times in mice with both early (day 7) and more advanced (day 14) levels
of tumor development. CD8+ T cell populations recovered
from spleens of tumor-bearing mice receiving Tc1 or Tc2 cells showed
markedly enhanced tumor Ag-specific cytolytic and cytokine-releasing
activities that correlated with delays in tumor cell growth and
progression. Initially, both tumor-reactive Tc1 and Tc2 effector cells
accumulated at the tumor site with nearly equal frequency. Tc1 cells
persisted, whereas Tc2 cell numbers progressively diminished over time.
Titration of Tc1 and Tc2 effector cells showed that protection was dose
dependent with the former being 5-fold more effective. Tc2 cells
achieved a comparable reduction in lung tumor cell growth at higher
concentrations of cell transfer. Tc1 effectors from IFN--deficient
mice were less therapeutically effective than wild-type mice, but there
was no significant reduction in activity between corresponding Tc2
populations. We speculate that the effectiveness of Tc1 and Tc2 cells
may depend on different mechanisms. These studies suggest a potential
role for Tc1 and Tc2 CD8+ subpopulations in tumor
regression and immunotherapy.
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