Impaired activation of islet-reactive CD4 T cells in pancreatic lymph nodes of B cell-deficient nonobese diabetic mice

S. A.W. Greeley, D. J. Moore, H. Noorchashm, L. E. Noto, S. Y. Rostami, A. Schlachterman, H. K. Song, B. Koeberlein, C. F. Barker, A. Naji

    Research output: Contribution to journalArticle

    52 Scopus citations

    Abstract

    Despite the impressive protection of B cell-deficient (μMT-/- nonobese diabetic (NOD) mice from spontaneous diabetes, existence of mild pancreatic islet inflammation in these mice indicates that initial autoimmune targeting of β cells has occurred. Furthermore, μMT-/- NOD mice are shown to harbor a latent repertoire of diabetogenic T cells, as evidenced by their susceptibility to cyclophosphamide-induced diabetes. The quiescence of this pool of islet-reactive T cells may be a consequence of impaired activation of T lymphocytes in B cell-deficient NOD mice. In this regard, in vitro anti-CD3- mediated stimulation demonstrates impaired activation of lymph node CD4 T cells in μMT-/- NOD mice as compared with that of wild-type counterparts, a deficiency that is correlated with an exaggerated CD4 T cell:APC ratio in lymph nodes of μMT-/- NOD mice. This feature points to an insufficient availability of APC costimulation on a per T cell basis, resulting in impaired CD4 T cell activation in lymph nodes of μMT-/- NOD mice. In accordance with these findings, an islet-reactive CD4 T cell clonotype undergoes suboptimal activation in pancreatic lymph nodes of μMT-/- NOD recipients. Overall, the present study indicates that B cells in the pancreatic lymph node microenvironment are critical in overcoming a checkpoint involving the provision of optimal costimulation to islet-reactive NOD CD4 T cells.

    Original languageEnglish (US)
    Pages (from-to)4351-4357
    Number of pages7
    JournalJournal of Immunology
    Volume167
    Issue number8
    DOIs
    StatePublished - Oct 15 2001

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Fingerprint Dive into the research topics of 'Impaired activation of islet-reactive CD4 T cells in pancreatic lymph nodes of B cell-deficient nonobese diabetic mice'. Together they form a unique fingerprint.

  • Cite this

    Greeley, S. A. W., Moore, D. J., Noorchashm, H., Noto, L. E., Rostami, S. Y., Schlachterman, A., Song, H. K., Koeberlein, B., Barker, C. F., & Naji, A. (2001). Impaired activation of islet-reactive CD4 T cells in pancreatic lymph nodes of B cell-deficient nonobese diabetic mice. Journal of Immunology, 167(8), 4351-4357. https://doi.org/10.4049/jimmunol.167.8.4351