Tumor-specific Tc1, but not Tc2, cells deliver protective antitumor immunity

We investigated whether secretion of multiple cytokines by CD8(+) T cells i s associated with improved protection against tumor challenge. We show that antitumor immunity induced by immunization with dendritic cells and a MHC class I-binding tumor peptide are dependent on secretion of IFN-gamma but n ot IL-4 or IL-5 by host cells. To further address the role of IL-4 and IL-5 in antitumor immunity, tumor-specific TCR-transgenic CD8(+) T cells were a ctivated in vitro to generate cytotoxic T (Tc) 1 cells that secrete high IF N-gamma and no IL-4 or IL-5 or Tc2 cells that secrete IL-4, IL-5, and some IFN-gamma. Both cell types killed target cells in vitro. Tc1 and Tc2 cells were adoptively transferred into syngeneic hosts, and their ability to prot ect against tumor challenge was compared. Tc1 cells were able to significan tly delay tumor growth, whereas Tc2 cells or Tc2 cells from IFN-gamma (-/-) donors had no effect. This was due to neither the inability of Tc2 cells t o survive in vivo or to migrate to the tumor site nor their inability to se crete IL-4 and/or IL-5 in the presence of limiting amounts of anti-CD3. How ever, IFN-gamma secretion by Tc2 cells was triggered inefficiently by resti mulation with Ag compared with anti-CD3. We conclude that the ability to se crete "type 2" cytokines, and cytotoxic ability, have a limited role in ant itumor immune responses mediated by CD8(+) T cells, whereas the capacity to secrete high amounts of IFN-gamma remains the most critical antitumor effe ctor mechanism in vivo.