Human Tc1 and Tc2/Tc0 CD8 T-cell clones display distinct cell surface and functional phenotypes

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-gamma (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)