ITK and IL-15 support two distinct subsets of CD8+ T cells.

CD8+ T cells are commonly divided into naïve CD44loCD122lo and ‘memory phenotype’ CD44hiCD122hi cells. Here we show data suggesting that these two cell populations represent independent CD8+ T cell subsets. Whereas IL-15-/- mice lack CD44hiCD122hi CD8+ T cells, mice deficient in the kinase ITK lack CD44loCD122lo cells among CD8+ T cells. The same defects were observed during thymus development. CD44hiCD122hi cells were found among double-positive thymocytes and increased in frequency during CD8 development in wild-type mice. At the mature stage, IL-15-/- mice harbored virtually no CD44hiCD122hi CD8+ thymocytes. In contrast, ITK-/- mice lacked CD44loCD122lo CD8+ cells at this stage. We generated mice with genetic deletions in both IL-15 and ITK and observed a severe reduction of all CD8+ T cells. The two CD44loCD122lo and CD44hiCD122hi CD8+ T cell subsets differed in the periphery in that natural killer (NK) receptor expression was found only on CD44hiCD122hi CD8+ T cells. This expression was paralleled by their ability to respond to both T cell receptor and NK receptor engagements. In contrast, CD44loCD122lo CD8+ T cells mounted stronger responses to T cell receptor stimulation but failed to recognize NK receptor ligands. Thus, whereas ITK-dependent CD44loCD122lo CD8+ T cells appear to represent conventional CD8+ T cells, IL-15-dependent CD44hiCD122hi CD8+ T cells may have functions in both adaptive and innate immunity. [ABSTRACT FROM AUTHOR]