BOTH T(H)1 AND T(H)2 CYTOKINE MESSENGER-RNAS ARE EXPRESSED IN THE NODMOUSE PANCREAS IN-VIVO

In NOD mice, autoimmune recognition and destruction of pancreatic isle t p-cells appear to be independently regulated: all mice develop cellu lar infiltration of the islets (insulitis), but not all develop diabet es. The destructive potential of the insulitis lesion may depend on th e balance between the two CD4(+) T-cell subsets, T(H)1 and T(H)2, that mediate cellular-cytotoxic and humoral responses, respectively. With a semi-quantiative reverse transcriptase-PCR assay, we examined whethe r the disease process was reflected in the profiles of T(H)1 (IL-2, IF N-gamma and IL-12) and T(H)2 (IL-4, IL-6 and IL-10) cytokine mRNAs exp ressed in pancreata of NOD mice. Pancreata rather than isolated islets were examined to minimize manipulation ex vivo to preserve the expres sion of cytokine transcripts in vivo. At age 6 weeks, when 70% of mice had insulitis, all cytokine transcripts were detected in most pancrea ta, and their expression levels corresponded to the degree of insuliti s. Similarly, during induction of diabetes with cyclophosphamide all t ranscripts were detected and levels corresponded with the degree of in sulitis. In one-year-old mice without diabetes, all transcripts were d etected but levels did not correspond to the degree of insulitis. Thus , in pancreata of NOD mice with different degrees of insulitis, we wer e unable to demonstrate, at the RNA level, polarisation of cytokine ex pression into either a T(H)1 or T(H)2 profile. This finding does not, however, exclude expression of distinct cytokine transcripts by immuno -inflammatory cells within the islet lesion, which might be revealed b y in situ hybridization.