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Blood, Vol. 95 No. 1 (January 1), 2000:
pp. 231-240
Human Tc1 and Tc2/Tc0 CD8 T-cell clones display distinct cell
surface and functional phenotypes
Milica Vukmanovic-Stejic,
Beejal Vyas,
Patricia Gorak-Stolinska,
Alistair Noble, and
David M. Kemeny
From the Department of Immunology, Guy's, King's, and St. Thomas'
School of Medicine, Rayne Institute, London, United Kingdom.
It has recently become clear that distinct subsets of CD8 T cells,
analogous to their CD4 counterparts, exist in rodents and humans. To
examine functional differences between human CD8 T-cell subsets, we
generated Tc1, Tc2, and Tc0 T-cell clones from the peripheral blood of
healthy individuals. The majority of CD8 T-cell clones generated
displayed a classic Tc1 phenotype, but 10% to 20% secreted
interleukin (IL)-4 in addition to interferon- (Tc0 phenotype).
Generation of Tc2 clones was dependent on the use of anti-CD3 and
anti-CD28 as the primary stimulus. The cytokine profiles of established
clones remained susceptible to modification by the addition of IL-12
and IL-4. In addition, IL-12 enhanced and IL-4 inhibited the growth of
Tc1 but not Tc2/0 CD8 T-cell clones. Significant functional differences
were observed between the subsets. Tc2/0 clones expressed CD30 and CD40
ligand at a much higher level than Tc1 clones. Both Tc1 and Tc2/0
clones showed comparable cytotoxicity and produced similar levels of
perforin and Fas L. However, Tc2 clones were much more resistant to
activation-induced cell death and less susceptible to
apoptosis by direct Fas ligation. Moreover, Tc1 and Tc2 clones had
opposing effects on the development of CD4 effectors, promoting type 1 and type 2 responses, respectively. These data provide evidence for
profound differences between human CD8 T-cell subsets that may be
important in their functions as cytotoxic or immunoregulatory cells.
(Blood. 2000;95:231-240)
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