A unique thymic fibroblast population revealed by the monoclonal antibody MTS-15

Daniel Herbert Donald Gray, Dedreia Tull, Tomoo Ueno, Natalie Louise Seach, Brendan J Classon, Ann P Chidgey, Malcolm J McConville, Richard Lennox Boyd

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    Abstract

    T cell differentiation in the thymus is dependent upon signals from thymic stromal cells. Most studies into the nature of these signals have focused only on the support provided by the thymic epithelium, but there is an emerging view that other stromal cells such as mesenchymal fibroblasts may also be involved. Study of the latter has been hindered by a lack of appropriate markers, particularly those allowing their isolation. In this study, we describe a new surface marker of thymic stroma, MTS-15, and demonstrate its specificity for fibroblasts and a subset of endothelial cells. Coculture experiments showed that the determinant could be transferred between cells. Extensive biochemical analysis demonstrated that the Ag bound by MTS-15 was the glycosphingolipid Forssman determinant, consistent with the distribution observed. Transcriptional analysis of purified MTS-15(+) thymic fibroblasts revealed a unique expression profile for a number of chemokines and growth factors important to thymocyte and epithelial cell development. In a model of cyclophosphamide-induced thymic involution and regeneration, fibroblasts were found to expand extensively and express growth factors important to epithelial proliferation and increased T cell production just before thymic regeneration. Overall, this study identifies a useful marker of thymic fibroblasts and highlights this subpopulation as a key player in thymic function by virtue of their support of both thymocytes and epithelial cells.
    Original languageEnglish
    Pages (from-to)4956 - 4965
    Number of pages10
    JournalJournal of Immunology
    Volume178
    Issue number8
    Publication statusPublished - 2007

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