Both TH1 and TH2 cytokine mRNAs are expressed in the NOD mouse pancreas in vivo.
In NOD mice, autoimmune recognition and destruction of pancreatic islet beta-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. TH1 and TH2, that mediate cellular-cytotoxic and humoral responses, respectively. With a semi-quantitative reverse transcriptase-PCR assay, we examined whether the disease process was reflected in the profiles of TH1 (IL-2, IFN-gamma and IL-12) and TH2 (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 TH1 or TH2 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.
Faulkner-Jones
B E
BE
Burnet Clinical Research Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Dempsey-Collier
M
M
Mandel
T E
TE
Harrison
L C
LC
D000375:Aging / Q000276:immunology; D000818:Animals; D003520:Cyclophosphamide / Q000633:toxicity; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced; D005260:Female; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis*; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
D016207:Cytokines; D012333:RNA, Messenger; D003520:Cyclophosphamide