Suppression of @entity12011 by viral XXXX gene transfer.

@entity12011 @entity6 @entity19 @entity13358 @entity146 @entity1618 @entity61 @entity792 @entity2025 @entity630
@entity630 cell activation and cytokine production shift the balance between @entity630 and @entity61 , favoring the up-regulation of proinflammatory activity that leads to destruction of insulin-producing pancreatic beta cells in type 1 @entity6 . @entity61 -type cytokines, such as @entity1618 , have immune regulatory function. Administration of @entity1618 , or @entity1618 gene transfer, prevents @entity12011 in nonobese @entity6 (NOD) @entity19 . However, constant administration of purified @entity13358 is not practical for long-term therapy to prevent @entity6 . In this study, we transferred the BCRF-1 gene, an open reading frame in the @entity2025 with remarkable homology to @entity19 @entity1618 (viral @entity1618 or vIL-10), by an adeno-associated viral (AAV) vector to NOD @entity19 to attain sustained vIL-10 gene expression. Like endogenous @entity19 @entity1618 , vIL-10 has potent immunoregulatory and immunosuppressive functions, but can be specifically distinguished from endogenous @entity19 @entity1618 for monitoring of the transgene expression. A single systemic administration of AAV vIL-10 significantly @entity146 and prevented @entity6 development in NOD @entity19 . This protective effect correlated with sustained transgene expression and protein production. Moreover, splenocytes from the treated @entity19 blocked @entity6 transfer to NOD recipients, suggesting that vIL-10 induces an active suppression of @entity792 . This study provides evidence to support the possibility of using vIL-10 gene therapy to prevent type 1 @entity6 .
