ITK and IL-15 support two distinct subsets of CD8+ T cells.
CD8(+) T cells are commonly divided into naïve CD44(lo)CD122(lo) and "memory phenotype" CD44(hi)CD122(hi) cells. Here we show data suggesting that these two cell populations represent independent CD8(+) T cell subsets. Whereas IL-15(-/-) mice lack CD44(hi)CD122(hi) CD8(+) T cells, mice deficient in the kinase ITK lack CD44(lo)CD122(lo) cells among CD8(+) T cells. The same defects were observed during thymus development. CD44(hi)CD122(hi) 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 CD44(hi)CD122(hi) CD8(+) thymocytes. In contrast, ITK(-/-) mice lacked CD44(lo)CD122(lo) 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 CD44(lo)CD122(lo) and CD44(hi)CD122(hi) CD8(+) T cell subsets differed in the periphery in that natural killer (NK) receptor expression was found only on CD44(hi)CD122(hi) CD8(+) T cells. This expression was paralleled by their ability to respond to both T cell receptor and NK receptor engagements. In contrast, CD44(lo)CD122(lo) CD8(+) T cells mounted stronger responses to T cell receptor stimulation but failed to recognize NK receptor ligands. Thus, whereas ITK-dependent CD44(lo)CD122(lo) CD8(+) T cells appear to represent conventional CD8(+) T cells, IL-15-dependent CD44(hi)CD122(hi) CD8(+) T cells may have functions in both adaptive and innate immunity.
Dubois
Sigrid
S
Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Waldmann
Thomas A
TA
Müller
Jürgen R
JR
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D049109:Cell Proliferation; D017353:Gene Deletion; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D019409:Interleukin-15 / Q000378:metabolism / Q000502:physiology*; D016131:Lymphocyte Subsets; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism
D018960:Hyaluronan Receptors; D019409:Interleukin-15; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase