Analysis of CD4+ automimmune T and CD45+ hematopoeitic cells from non-obese diabetic (NOD) and C57BL/6-H-2 g7 transgenics with the BDC2.5 T cell receptor (TCR) from a diabetogenic T cell. BDC2.5 TCR in NOD and in C57BL/6-H-2 g7 results in innocuous and destructive insulitis respectively.

Delineate the molecular and cellular mechanisms underlying innocuous/benign versus destructive/aggressive insulitis as the latter leads to diabetes.

Microarray analysis was performed on flow cytometry-sorted immune cell populations from BDC2.5/NOD (benign model for insulitis) and BDC2.5/B6.H-2g7 mice (aggressive model for insulitis) using the Affymetrix Mu74Av2 array. Key findings were confirmed by RT-PCR and flow cytometry.

Leukocytes from pancreas in B6.H-2g7 (aggressive insulitis) mice were enriched in transcripts from natural killer cells (NKC) as compared to leukocytes from NOD (benign insulitis) mice. Comparison of spleen NKC from the two backgrounds revealed differences in expression in Ly49m, Ly49h, Ly49c, Nkrp1a, Nkrp1c suggesting that variation in NKC gene expression also contributes to type of insulitis.

Increased frequency of natural killer cells is correlated with aggressive insulitis leading to diabetes. Furthermore variation in NKC gene expression can also contribute to differences in insulitis.

• NOD mice: 2000, 2421, 2424, 2440, 3144,