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Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells

  1. Author:
    Park, J. H.
    Adoro, S.
    Guinter, T.
    Erman, B.
    Alag, A. S.
    Catalfamo, M.
    Kimura, M. Y.
    Cui, Y. Z.
    Lucas, P. J.
    Gress, R. E.
    Kubo, M.
    Hennighausen, L.
    Feigenbaum, L.
    Singer, A.

  2. Author Address

    [Park, Jung-Hyun; Adoro, Stanley; Guinter, Terry; Alag, Amala S.; Kimura, Motoko Y.; Singer, Alfred] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Erman, Batu] Sabanci Univ, Biol Sci & Bioengn Program, Fac Engn & Nat Sci, Istanbul, Turkey. [Catalfamo, Marta] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. [Cui, Yongzhi; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD USA. [Lucas, Philip J.; Gress, Ronald E.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Kubo, Masato] RIKEN, Yokohama Inst, Lab Signal Network, Res Ctr Allergy & Immunol, Kanagawa, Japan. [Feigenbaum, Lionel] NCI, Sci Applicat Int Corp Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD USA.;Singer, A, NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.;singera@mail.nih.gov
    1. Year: 2010
    2. Date: Mar
  2. Journal: Nature Immunology
    1. 11
    2. 3
    3. Pages: 257-U10
  4. Type of Article: Article
  5. ISSN: 1529-2908
  1. Abstract:

    Immature CD4(+) CD8(+) (double-positive (DP)) thymocytes are signaled via T cell antigen receptors (TCRs) to undergo positive selection and become responsive to intrathymic cytokines such as interleukin 7 (IL-7). We report here that cytokine signaling is required for positively selected thymocytes to express the transcription factor Runx3, specify CD8 lineage choice and differentiate into cytotoxic-lineage T cells. In DP thymocytes genetically engineered to be cytokine responsive, IL-7 signaling induced TCR-unsignaled DP thymocytes to express Runx3 and to differentiate into mature CD8(+) T cells, completely circumventing positive selection. We conclude that TCR-mediated positive selection converts DP cells into cytokine-responsive thymocytes, but it is subsequent signaling by intrathymic cytokines that specifies CD8 lineage choice and promotes differentiation into cytotoxic-lineage T cells.

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External Sources

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  2. DOI: 10.1038/ni.1840
  3. View record in Web of Science®
  4. WOS: 000274605800014

Library Notes

  1. Fiscal Year: FY2009-2010
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