The effect of adjuvants on immune function in the multi-low-dose streptozotocin model of murine diabetes.

The effect of various adjuvants has been investigated on the multi-low-dose (mld) streptozotocin (STZ) model of diabetes in C57BL/6 and CBA mice; diabetes was severe in the former strain. Diabetic levels of glycaemia were not attained in either strain using half the mld STZ dose (sub-mld-STZ). The adjuvants were found to affect the levels of glycaemia variously. Thus, in C57BL/6 mice at mld-STZ, CFA and saponin had no effect, whereas MDP and LPS respectively decreased and increased glycaemia; at sub-mld-STZ, each of the adjuvants increased glycaemia. In CBA mice, at both mld- and sub-mld-STZ, CFA and saponin increased glycaemia; at mld-STZ, MDP caused an initial increase but a later decrease in glycaemia, whereas with sub-mld-STZ only a decrease in glycaemia occurred; at mld-STZ, LPS was toxic in this strain, and had no effect on glycaemia at sub-mld-STZ. In both C57BL/6 and CBA mice, STZ caused a decrease in both spontaneous and PHA-stimulated blastogenesis. This persisted until day 14 in the C57BL/6 strain and until day 28 in the CBA strain. CFA reversed the anergy by day 7 in C57BL/6 mice and by day 14 in CBA mice, but did not improve beta-cell function, since further increments in glycaemia followed, except in mld-STZ C57BL/6 mice. Islet-cell surface antibodies (ICSAs) and cytotoxic islet-cell antibodies (CxICAs) occurred in both strains of mouse. ICSAs were persistent (still present at day 67), but CxICAs were detected only until day 23. The presence of ICSAs and CxICAs during the development of the diabetic state, and of ICSAs during its perpetuation, suggests that they may have a role in its aetiopathology. The lack of a correlation of non-specific T-cell anergy with glycaemia does not exclude a role for antigen-specific T-cell pathogenic processes.