Both T_H1 and T_H2 Cytokine mRNAs are Expressed in the NOD Mouse Pancreas in vivo

Abstract

In NOD mice, autoimmune recognition and destruction of pancreatic islet β-cells appear to be independently regulated: all mice develop cellular infiltration of the islets (insulitis), but not all develop diabetes. The destructive potential of the insulitis lesion may depend on the balance between the two CD4⁺ T-cell subsets, T_H1 and T_H2, that mediate cellular-cytotoxic and humoral responses, respectively. With a semiquantiative reverse transcriptase-PCR assay, we examined whether the disease process was reflected in the profiles of T_H1 (IL-2, IFN-γ and IL-12) and T_H2 (IL-4, IL-6 and IL-10) cytokine mRNAs expressed in pancreata of NOD mice. Pancreata rather than isolated islets were examined to minimize manipulation ex vivo to preserve the expression of cytokine transcripts in vivo.

At age 6 weeks, when 70% of mice had insulitis, all cytokine transcripts were detected in most pancreata, and their expression levels corresponded to the degree of insulitis. Similarly, during induction of diabetes with cyclophosphamide all transcripts were detected and levels corresponded with the degree of insulitis. In one-year-old mice without diabetes, all transcripts were detected but levels did not correspond to the degree of insulitis.

Thus, in pancreata of NOD mice with different degrees of insulitis, we were unable to demonstrate, at the RNA level, polarisation of cytokine expression into either a T_H1 or T_H2 profile. This finding does not, however, exclude expression of distinct cytokine transcripts by immuno-inflammatory cells within the islet lesion, which might be revealed by in situ hybridization.

Key Words:

• NOD mouse
• pancreas
• islets
• cytokine mRNA
• T_H1
• T_H2
• cyclophosphamide