Saw. Greeley et al., Impaired activation of islet-reactive CD4 T cells in pancreatic lymph nodes of B cell-deficient nonobese diabetic mice, J IMMUNOL, 167(8), 2001, pp. 4351-4357
Despite the impressive protection of B cell-deficient (mu MT-/-) nonobese d
iabetic (NOD) mice from spontaneous diabetes, existence of mild pancreatic
islet inflammation in these mice indicates that initial autoimmune targetin
g of beta cells has occurred. Furthermore, mu MT-/- NOD mice are shown to h
arbor a latent repertoire of diabetogenic T cells, as evidenced by their su
sceptibility to cyclophosphamide-induced diabetes. The quiescence of this p
ool of islet-reactive T cells may be a consequence of impaired activation o
f T lymphocytes in B cell-deficient NOD mice. In this regard, in vitro anti
-CD3-mediated stimulation demonstrates impaired activation of lymph node CD
4 T cells in mu MT-/- NOD mice as compared with that of wild-type counterpa
rts, a deficiency that is correlated with an exaggerated CD4 T cell:APC rat
io in lymph nodes of mu MT-/- NOD mice. This feature points to an Insuffici
ent availability of APC costimulation on a per T cell basis, resulting in i
mpaired CD4 T cell activation in lymph nodes of mu MT-/- NOD mice. In accor
dance with these findings, an islet-reactive CD4 T cell clonotype undergoes
suboptimal activation in pancreatic lymph nodes of mu MT-/- NOD recipients
. Overall, the present study indicates that B cells in the pancreatic lymph
node microenvironment are critical in overcoming a checkpoint involving th
e provision of optimal costimulation to islet-reactive NOD CD4 T cells.