B cell-adherent splenocytes precede the onset of diabetes in low-dose streptozotocin-treated mice.
Splenocytes from low-dose (40 mg.kg-1.day-1) streptozotocin-treated mice were tested for their binding ability to rat insulinoma (RINm-5F) cells in a rosette-forming cell assay, before and during the onset of diabetes. They displayed a higher (p less than 0.0001) RIN-adherence than control splenocytes. Such an enhanced binding of splenocytes from diabetic mice was observed on another B-cell (HIT cell) line, but not on non-B cells (particularly on exocrine pancreatic cells, endocrine cells or natural killer-target cells), suggesting that the increased RIN-binding is B-cell specific. This B-cell specificity was also suggested by the use of increasing splenocytes/RIN ratios showing a saturation of RIN-binding in streptozotocin-treated mice. Depletion of lymphocyte subsets revealed that supernumerary RIN-adherent splenocytes from diabetic mice were mainly T lymphocytes, involving both L3T4+ and Lyt2+ cells. Overall, the increased splenocyte-RIN binding was concomitant with the occurrence of islet destruction, but preceded the onset of hyperglycaemia by five days and even the islet immune infiltration. An increased number of RIN-binding splenocytes was also found in mice treated with 33 mg.kg-1.day-1 of streptozotocin, displaying insulitis but not hyperglycaemia. This phenomenon was not found with splenocytes from mice displaying a "toxic" diabetes induced by a single high dose of streptozotocin. No correlation could thus be found between numbers of RIN-binding splenocytes and blood glucose levels, indicating that this phenomenon was not due to metabolic disturbances. These data describe a new marker of cellular immunity in this animal model.(ABSTRACT TRUNCATED AT 250 WORDS)
Feve
B
B
Laboratoire d'immunologie du diabete, Faculté de Médecine, Nantes, France.
Segain
J P
JP
Charbonnel
B
B
Sai
P
P
D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D007111:Immunity, Cellular; D007340:Insulinoma / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010190:Pancreatic Neoplasms / Q000276:immunology; D011236:Prediabetic State / Q000276:immunology*; D051381:Rats; D012397:Rosette Formation; D013154:Spleen / Q000276:immunology*; D013311:Streptozocin / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology
D013311:Streptozocin