Specialized CC-chemokine secretion by Th1 cells in destructive autoimmune myocarditis

Howard K. Song, Hooman Noorchashm, Tina H. Lin, Daniel J. Moore, Siri A. Greeley, Andrew J. Caton, Ali Naji

    Research output: Contribution to journalArticle

    16 Scopus citations

    Abstract

    T helper (Th) 1-mediated immune responses are associated with adverse outcomes in a number of models of autoimmune disease. Previous work has focused on the role that cytokines secreted by Th1 cells play in mediating pathologic tissue injury. To evaluate other mechanisms by which Th1 cells may be specialized to coordinate the complex effector cell interactions of a destructive immune response, CD4+ T cells specific for influenza hemagglutinin (HA) were differentiated into Th1 or Th2 subsets and transferred into transgenic mice expressing HA under control of the β myosin heavy chain promoter, which drives heart specific expression of HA. CD4+ T cells polarized to a Th1 phenotype mediated a more destructive myocarditis than Th2 cells. Strikingly, the Th1-mediated inflammation was comprised primarily of CD8+ T cells and macrophages, suggesting a specialized recruitment function for Th1 cells. Further studies revealed that Th1 and Th2 subsets had polarized secretion of certain CC-chemokines, including MIP-1α and RANTES, which have selective recruitment properties on effector cells. Th1 cell secreted factors were up to 1000-fold more potent in inducing CD8+ T cell migration compared to Th2 cell secreted factors, and this advantage was partially mediated by their specialized MIP-1α secretion. These findings indicate that Th subsets have distinct patterns of CC-chemokine secretion and this specialization by Th1 cells mediates the recruitment of cytotoxic effector cells into destructive inflammatory responses.

    Original languageEnglish (US)
    Pages (from-to)295-303
    Number of pages9
    JournalJournal of Autoimmunity
    Volume21
    Issue number4
    DOIs
    StatePublished - Dec 2003

    Keywords

    • Autoimmunity
    • C-C chemokines
    • Myocarditis
    • T cells
    • T helper subsets

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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  • Cite this

    Song, H. K., Noorchashm, H., Lin, T. H., Moore, D. J., Greeley, S. A., Caton, A. J., & Naji, A. (2003). Specialized CC-chemokine secretion by Th1 cells in destructive autoimmune myocarditis. Journal of Autoimmunity, 21(4), 295-303. https://doi.org/10.1016/S0896-8411(03)00110-0