Multiple low-dose streptozocin-induced diabetes in NOD-scid/scid mice in the absence of functional lymphocytes.
The murine severe combined immunodeficiency (scid) mutation was used to assess whether the diabetogenic effects of multiple low-dose streptozocin (MD-STZ) administration required the presence of functional T-cells. An STZ dose as low as 30 mg/kg body wt for 5 days induced hyperglycemia in young NOD/Lt-+/+ male mice, whereas a dose of 50 mg/kg for 5 days was required to elicit comparable hyperglycemia in C.B.-17-+/+ male mice. The greater NOD strain sensitivity was not a function of preexisting insulitis, because insulitis- and diabetes-free NOD male mice congenic for a diabetes-resistant major histocompatibility complex haplotype were equally susceptible to MD-STZ. This was confirmed in NOD-scid/scid and C.B.-17-scid/scid males. Both were completely insulitis-free, and despite the absence of functional T- cells and B-cells, both congenic stocks were as sensitive to MD-STZ as congenic +/+ controls. Indeed, MD-STZ-induced hyperglycemia in NOD-scid/scid male mice was significantly higher than in NOD/Lt-+/+ male mice. The NOD-scid/scid mouse as a recipient of adoptively transferred splenocytes clearly delineated a distinct pathogenesis of spontaneous insulin-dependent diabetes mellitus (IDDM) versus MD-STZ-induced hyperglycemia. Splenocytes from spontaneously diabetic NOD/Lt males, but not those from donors given MD-STZ, readily transferred IDDM, even when host beta-cells were sensitized by a single injection of STZ before adoptive transfer. We conclude that IDDM induced by MD-STZ is not mediated by T-cell- or B-cell-dependent autoimmune mechanisms in a fashion analogous to the spontaneous IDDM characteristic of NOD mice.
Gerling
I C
IC
Jackson Laboratory, Bar Harbor, ME 04609.
Friedman
H
H
Greiner
D L
DL
Shultz
L D
LD
Leiter
E H
EH
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002467:Cell Nucleus / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013154:Spleen / Q000166:cytology; D013311:Streptozocin / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000502:physiology* / Q000637:transplantation
D001786:Blood Glucose; D013311:Streptozocin