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*
Trudeau Institute, Saranac Lake, NY 12983; and
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110
Naive CD8 T cells can be polarized into effectors producing the
type 1 cytokines IFN-
and IL-2 or the type 2 cytokines IL-4, IL-5,
and IL-10, respectively. To study whether the polarized cytokine
phenotype of the effectors is stable, we generated highly cytotoxic
hemagglutinin (HA) peptide-specific CD8 Tc1 and Tc2 (cytotoxic CD8 T
cells producing type 1 or type 2 cytokines) effectors from Clone-4
TCR-transgenic mice, which were adoptively transferred into syngeneic
adult thymectomized irradiated and bone marrow-reconstituted
recipients. The highly activated blast-size, CD25+
Tc1 and Tc2 effectors gave rise to homogeneous resting
CD25-CD44highLy6Chigh Ag-specific
populations, which persisted for at least 13 wk after adoptive
transfer. These memory CD8 T cells, recovered 13 wk after transfer of
Tc1 or Tc2 effectors, still produced either the type 1 or type 2
cytokines, i.e., IFN-
, or IL-4 and IL-5, respectively, upon
restimulation with APCs loaded with the HA peptide, but not in the
absence of Ag. The amounts of IL-2 detected in the supernatants of Tc1
and Tc2 memory populations were comparable to that in memory CD4 cells,
and both Tc1 and Tc2 memory cells became cytotoxic upon restimulation.
Thus, cytokine-polarized CD8 memory T cells are a source of a variety
of cytokines, which were classically considered helper cytokines,
opening new perspectives on their function as regulatory cells in an
immune response.
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