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    Differential antitumor immunity mediated by NKT cell subsets in vivo

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    Author
    Crowe, NY; Coquet, JM; Berzins, SP; Kyparissoudis, K; Keating, R; Pellicci, DG; Hayakawa, Y; Godfrey, DI; Smyth, MJ
    Date
    2005-11-07
    Source Title
    JOURNAL OF EXPERIMENTAL MEDICINE
    Publisher
    ROCKEFELLER UNIV PRESS
    University of Melbourne Author/s
    CROWE, NADINE; Berzins, Stuart; Pellicci, Daniel; Godfrey, Dale; SMYTH, MARK; KYPARISSOUDIS, KONSTANTINOS; COQUET, JONATHAN MARIE CHRISTIAN
    Affiliation
    Pathology
    Metadata
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    Document Type
    Journal Article
    Citations
    Crowe, N. Y., Coquet, J. M., Berzins, S. P., Kyparissoudis, K., Keating, R., Pellicci, D. G., Hayakawa, Y., Godfrey, D. I. & Smyth, M. J. (2005). Differential antitumor immunity mediated by NKT cell subsets in vivo. JOURNAL OF EXPERIMENTAL MEDICINE, 202 (9), pp.1279-1288. https://doi.org/10.1084/jem.20050953.
    Access Status
    Access this item via the Open Access location
    URI
    http://hdl.handle.net/11343/26148
    DOI
    10.1084/jem.20050953
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459911
    Description

    C1 - Journal Articles Refereed

    Abstract
    We showed previously that NKT cell-deficient TCR Jalpha18(-/-) mice are more susceptible to methylcholanthrene (MCA)-induced sarcomas, and that normal tumor surveillance can be restored by adoptive transfer of WT liver-derived NKT cells. Liver-derived NKT cells were used in these studies because of their relative abundance in this organ, and it was assumed that they were representative of NKT cells from other sites. We compared NKT cells from liver, thymus, and spleen for their ability to mediate rejection of the sarcoma cell line (MCA-1) in vivo, and found that this was a specialized function of liver-derived NKT cells. Furthermore, when CD4(+) and CD4(-) liver-derived NKT cells were administered separately, MCA-1 rejection was mediated primarily by the CD4(-) fraction. Very similar results were achieved using the B16F10 melanoma metastasis model, which requires NKT cell stimulation with alpha-galactosylceramide. The impaired ability of thymus-derived NKT cells was due, in part, to their production of IL-4, because tumor immunity was clearly enhanced after transfer of IL-4-deficient thymus-derived NKT cells. This is the first study to demonstrate the existence of functionally distinct NKT cell subsets in vivo and may shed light on the long-appreciated paradox that NKT cells function as immunosuppressive cells in some disease models, whereas they promote cell-mediated immunity in others.
    Keywords
    Cellular Immunology; Immune System and Allergy

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