Treatment with non-depleting T cell antibodies increases TGFβ levels in the diabetic pancreas and results in enhanced β cell function. (P5213)

Abstract

Abstract A recent report from our laboratory detailed the reversal of recent-onset autoimmune diabetes in the NOD mouse following treatments with antibodies against CD4 and CD8. Treatment of mice with these particular antibodies does not deplete T cells, but transiently alters their function, culminating in long-lasting immune tolerance and a restoration of normal glycemic control. Consistent with observations made by other research groups, induction of diabetes remission was dependent on TGFβ, supported by two lines of evidence: 1 - co-administration of anti-TGFβ with anti-T cell antibodies resulted in a failure of remission induction, and 2 - elevated levels of TGFβ RNA and protein can be detected in the pancreata of remission mice. Within one week of antibody treatment, T cells are purged from the pancreas and the draining lymph node in a process that was found to be independent of TGFβ, suggesting that effects of elevated TGFβ are not limited to T cell function. Furthermore, treatment of recent-onset diabetic mice with a reduced dose of antibody resulted in a purging of T cells from the pancreas and draining lymph node, but not a restoration of glycemic control. Normal glycemic control could be achieved at this dose when exogenous TGFβ was administered. Together, these data indicate that TGFβ may directly affect the insulin-producing pancreatic β cells. Recent observations support the notion that TGFβ enhances insulin production and/or induces β cell proliferation.