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Trudeau Institute, Saranac Lake, NY 12983
Cytolytic CD8+ effector cells fall into two
subpopulations based on cytokine secretion. Type 1 CD8+ T
cells (Tc1) secrete IFN-
, whereas type 2 CD8+ T cells
(Tc2) secrete IL-4, IL-5, and IL-10. Using an OVA-transfected B16 lung
metastases model, we assessed the therapeutic effects of adoptively
transferred OVA-specific Tc1 and Tc2 subpopulations in mice bearing
established pulmonary malignancy. Effector cell-treated mice exhibiting
high (5 x 105) tumor burdens experienced significant
(p < 0.05) delays in mortality compared with those
of untreated control mice, whereas high proportions (70–90%) of mice
receiving therapy with low (1 x 105) tumor burdens
survived indefinitely. Long-term tumor immunity was evident by
resistance to lethal tumor rechallenge, heightened levels of systemic
OVA Ag-specific CTL responses ex vivo, and detection of long-lived TCR
transgene-positive donor cells accompanied by an elevation in the total
numbers of CD8+ CD44high activated and/or
memory T cells at sites of tumor growth. Long-lasting protection by Tc2
and Tc1 effector cells were dependent, in part, on both the level of
tumor burden and effector cell-derived IL-4, IL-5, and IFN-,
respectively. We conclude that Tc1 and Tc2 effector cells provide
immunity by different mechanisms that subsequently potentiate
host-derived antitumor responses.
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