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, Howard Song, B. Koeberlein, C. F. Barker, A. Naji

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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
Publication statusPublished - Oct 15 2001
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Greeley, S. A. W., Moore, D. J., Noorchashm, H., Noto, L. E., Rostami, S. Y., Schlachterman, A., ... 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.