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

Research output: Contribution to journalArticle

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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
StatePublished - Oct 15 2001
Externally publishedYes

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Inbred NOD Mouse
B-Lymphocytes
Lymph Nodes
T-Lymphocytes
Insulin-Secreting Cells
Islets of Langerhans
Cyclophosphamide
Inflammation

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.

Impaired activation of islet-reactive CD4 T cells in pancreatic lymph nodes of B cell-deficient nonobese diabetic mice. / Greeley, S. A W; Moore, D. J.; Noorchashm, H.; Noto, L. E.; Rostami, S. Y.; Schlachterman, A.; Song, Howard; Koeberlein, B.; Barker, C. F.; Naji, A.

In: Journal of Immunology, Vol. 167, No. 8, 15.10.2001, p. 4351-4357.

Research output: Contribution to journalArticle

Greeley, SAW, Moore, DJ, Noorchashm, H, Noto, LE, Rostami, SY, Schlachterman, A, Song, H, Koeberlein, B, Barker, CF & 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, vol. 167, no. 8, pp. 4351-4357.
Greeley SAW, Moore DJ, Noorchashm H, Noto LE, Rostami SY, Schlachterman A et al. Impaired activation of islet-reactive CD4 T cells in pancreatic lymph nodes of B cell-deficient nonobese diabetic mice. Journal of Immunology. 2001 Oct 15;167(8):4351-4357.
Greeley, S. A W ; Moore, D. J. ; Noorchashm, H. ; Noto, L. E. ; Rostami, S. Y. ; Schlachterman, A. ; Song, Howard ; Koeberlein, B. ; Barker, C. F. ; Naji, A. / Impaired activation of islet-reactive CD4 T cells in pancreatic lymph nodes of B cell-deficient nonobese diabetic mice. In: Journal of Immunology. 2001 ; Vol. 167, No. 8. pp. 4351-4357.
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