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Malaghan Institute of Medical Research, Wellington School of Medicine, Wellington, New Zealand
We investigated whether secretion of multiple cytokines by
CD8+ T cells is 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-
but not 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
activated in vitro to generate cytotoxic T (Tc) 1 cells that secrete
high IFN- and no IL-4 or IL-5 or Tc2 cells that secrete IL-4, IL-5,
and some IFN-. Both cell types killed target cells in vitro. Tc1 and
Tc2 cells were adoptively transferred into syngeneic hosts, and their
ability to protect against tumor challenge was compared. Tc1 cells were
able to significantly delay tumor growth, whereas Tc2 cells or Tc2
cells from IFN--/- donors had no effect. This was due
to neither the inability of Tc2 cells to survive in vivo or to migrate
to the tumor site nor their inability to secrete IL-4 and/or IL-5 in
the presence of limiting amounts of anti-CD3. However, IFN-
secretion by Tc2 cells was triggered inefficiently by restimulation
with Ag compared with anti-CD3. We conclude that the ability to
secrete "type 2" cytokines, and cytotoxic ability, have a limited
role in antitumor immune responses mediated by CD8+ T
cells, whereas the capacity to secrete high amounts of IFN- remains
the most critical antitumor effector mechanism in
vivo.
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