In vitro IL-15-activated human naive CD8+T cells down-modulate the CD8β chain and become CD8αα T cells

Antigen-driven human effector-memory CD8+ T cells expressing low levels of the CD8 beta chain have been previously described. However, little is known on a possible antigen-independent trigger. We have examined the impact that IL-15 has on the expression of CD8 beta on purified human na & iuml;ve CD8+ T cells after CFSE labeling and culture with IL-15. As expected, IL-15 induced na & iuml;ve CD8+ T cells to proliferate and differentiate. Remarkably, the process was associated with a cell-cycle dependent down-modulation of CD8 beta from the cell surface, leading to the generation of CD8 alpha beta(low) and CD8 alpha beta(-) (i.e., CD8 alpha alpha) T cells. In contrast, expression of the CD8 alpha chain remained steady or even increased. Neither IL-2 nor IL-7 reproduced the effect of IL-15. Determination of mRNA levels for CD8 alpha and CD8 beta isoforms by qPCR revealed that IL-15 promoted a significant decrease in mRNA levels of the CD8 beta M-4 isoform, while levels of the M-1/M-2 isoforms and of CD8 alpha increased. Noteworthy, CD8+ T cell blasts obtained after culture of CD8+ T cells with IL-15 showed a cell-cycle dependent increase in the level of the tyrosine kinase Lck, when compared to CD8+ T cells at day 0. This study has shown for the first time that IL-15 generates CD8 alpha alpha(+)alpha beta(low) and CD8 alpha alpha(+)alpha beta(-) T cells containing high levels of Lck, suggesting that they may be endowed with unique functional features.