DOCK2 is required in T cell precursors for development of Vα14 NK T cells

Yuya Kunisaki, Yoshihiko Tanaka, Terukazu Sanui, Ayumi Inayoshi, Mayuko Noda, Toshinori Nakayama, Michishige Harada, Masaru Taniguchi, Takehiko Sasazuki, Yoshinori Fukui

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25 Citations (Scopus)

Abstract

Mouse CD1d-restricted Vα14 NKT cells are a unique subset of lymphocytes, which play important roles in immune regulation, tumor surveillance and host defense against pathogens. DOCK2, a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster myoblast city, is critical for lymphocyte migration and regulates T cell responsiveness through immunological synapse formation, yet its role in Vα14 NKT cells remains unknown. We found that DOCK2 deficiency causes marked reduction of Vα14 NKT cells in the thymus, liver, and spleen. When α-galactesylceramide (α-GalCer), a ligand for Vα14 NKT cells, was administrated, cytokine production was scarcely detected in DOCK2-deficient mice, suggesting that DOCK2 deficiency primarily affects generation of Vα14 NKT cells. Supporting this idea, staining with CD1d/α-GalCer tetramers revealed that CD44 -NK1.1- Vα14 NKT cell precursors are severely reduced in the thymuses of DOCK2-deficient mice. In addition, studies using bone marrow chimeras indicated that development of Vα14 NKT cells requires DOCK2 expression in T cell precursors, but not in APCs. These results indicate that DOCK2 is required for positive selection of Vα14 NKT cells in a cell-autonomous manner, thereby suggesting that avidity-based selection also governs development of this unique subset of lymphocytes in the thymus.

Original languageEnglish
Pages (from-to)4640-4645
Number of pages6
JournalJournal of Immunology
Volume176
Issue number8
Publication statusPublished - Apr 15 2006

All Science Journal Classification (ASJC) codes

  • Immunology

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    Kunisaki, Y., Tanaka, Y., Sanui, T., Inayoshi, A., Noda, M., Nakayama, T., Harada, M., Taniguchi, M., Sasazuki, T., & Fukui, Y. (2006). DOCK2 is required in T cell precursors for development of Vα14 NK T cells. Journal of Immunology, 176(8), 4640-4645.