Dialyzable lymphoid extract (DLE) from mice resistant to STZ-induced diabetogenesis can interrupt the progress of diabetes in STZ-treated CD-1 mice.
DLE was prepared from the minority of euglycemic CD-1 mice, previously injected with STZ, and was administered to hyperglycemic CD-1 male mice 1, 2 and 3 weeks after completion of multidose STZ. Mice treated with DLE derived from 2 x 10(7) (IX) or 10(8) lymphocyte equivalents (lymph.equ) were significantly less hyperglycemic than the saline treated controls (P < 0.001). The effects of DLE remained evident for more than 10 weeks after the final DLE treatment. Mice treated with DLE prepared from diabetic mice (hg DLE) developed a somewhat more rapid onset of hyperglycemia than the STZ treated control animals, although this effect did not achieve statistical significance (P = 0.1). This DLE was absorbed on a rat insulinoma cell line (RIN), which contains interspecies cross-reacting islet antigens, and compared to the unabsorbed DLE. Mice treated with hg DLE preabsorbed on RIN cells, showed a slower onset of hyperglycemia. DLE prepared from euglycemia mice and the RIN-absorbed fraction were equally capable of preventing hyperglycemia (P < 0.05). In order to determine whether the DLE effects were genetically restricted, DLE was prepared from BALB/c mice, normally resistant to the diabetogenic effects of multidose STZ, both before and after STZ treatment. STZ primed CD-1 mice treated with 3 weekly doses of 2 x 10(7) lymph. equ. of untreated BALB/c derived DLE, STZ treated BALB/c derived DLE, and STZ treated CD-1 DLE were all less hyperglycemic than the control mice, who received saline (P < 0.001). However, mice treated with CD-1 DLE were less hyperglycemic than the mice given BALB/c derived DLE (P < 0.05). These effects were relatively long-lived. Mice that were given the > 3,500 Dalton fraction of CD-1 DLE were significantly less hyperglycemic than either the control mice or those treated with the < 3,500 Dalton fraction of CD-1 DLE (P < 0.05). Effects remained evident for more than 3 months after the last dose of DLE. Pancreatic tissue from the mice treated with the > 3,500 Dalton fraction of CD-1 derived DLE revealed slightly more islets of a slightly greater size with less surrounding inflammation than either control mice or mice treated with the < 3,500 Dalton fraction of DLE.
Borkowsky
W
W
New York University Medical Center. Department of Paediatrics, New York, NY, USA.
Pilson
R
R
Lawrence
H S
HS
D000818:Animals; D002457:Cell Extracts / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D003956:Dialysis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007167:Immunotherapy; D008214:Lymphocytes / Q000737:chemistry / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D012680:Sensitivity and Specificity; D013491:Suppressor Factors, Immunologic / Q000494:pharmacology; D014165:Transfer Factor / Q000494:pharmacology*
D002457:Cell Extracts; D013491:Suppressor Factors, Immunologic; D014165:Transfer Factor