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Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
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 
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.
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