Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 32, Pages 12075-12080Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0605212103
Keywords
thymic development; T cell activation; NK receptors
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Funding
- Intramural NIH HHS Funding Source: Medline
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CD8(+) T cells are commonly divided into naive 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.
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