Open AccessITK and IL-15 support two distinct subsets of CD8+T cells
Author(s) -
Sigrid Dubois,
Thomas A. Waldmann,
Jürgen Müller
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0605212103
Subject(s) - cd44 , cd8 , biology , cytotoxic t cell , interleukin 21 , natural killer t cell , interleukin 12 , t cell , microbiology and biotechnology , immune system , cell , immunology , in vitro , genetics
CD8+ T cells are commonly divided into naïve CD44lo CD122lo and “memory phenotype” CD44hi CD122hi cells. Here we show data suggesting that these two cell populations represent independent CD8+ T cell subsets. Whereas IL-15−/− mice lack CD44hi CD122hi CD8+ T cells, mice deficient in the kinase ITK lack CD44lo CD122lo cells among CD8+ T cells. The same defects were observed during thymus development. CD44hi CD122hi 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 CD44hi CD122hi CD8+ thymocytes. In contrast, ITK−/− mice lacked CD44lo CD122lo 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 CD44lo CD122lo and CD44hi CD122hi CD8+ T cell subsets differed in the periphery in that natural killer (NK) receptor expression was found only on CD44hi CD122hi CD8+ T cells. This expression was paralleled by their ability to respond to both T cell receptor and NK receptor engagements. In contrast, CD44lo CD122lo CD8+ T cells mounted stronger responses to T cell receptor stimulation but failed to recognize NK receptor ligands. Thus, whereas ITK-dependent CD44lo CD122lo CD8+ T cells appear to represent conventional CD8+ T cells, IL-15-dependent CD44hi CD122hi CD8+ T cells may have functions in both adaptive and innate immunity.