Rabbit Polyclonal Mouse Antithymocyte Globulin Administration Alters Dendritic Cell Profile and Function in NOD Mice to Suppress Diabetogenic Responses

Content Provider	Scilit
Author	Huang, Yanfei Parker, Matthew Xia, Changqing Peng, Ruihua Wasserfall, Clive Clarke, Tracy Wu, Lizhen Chowdhry, Tayseer Campbell-Thompson, Martha Williams, John Clare-Salzler, Michael Atkinson, Mark A. Womer, Karl L.
Copyright Year	2009
Description	Mouse antithymocyte globulin (mATG) prevents, as well as reverses, type 1 diabetes in NOD mice, through mechanisms involving modulation of the immunoregulatory activities of T lymphocytes. Dendritic cells (DC) play a pivotal role in the generation of T cell responses, including those relevant to the autoreactive T cells enabling type 1 diabetes. As Abs against DC are likely generated during production of mATG, we examined the impact of this preparation on the phenotype and function of DC to elucidate novel mechanisms underlying its beneficial activities. In vivo, mATG treatment transiently induced the trafficking of mature $CD8^{−}$ predominant DC into the pancreatic lymph node of NOD mice. Splenic DC from mATG-treated mice also exhibited a more mature phenotype characterized by reduced CD8 expression and increased IL-10 production. The resultant DC possessed a potent capacity to induce Th2 responses when cultured ex vivo with diabetogenic $CD4^{+}$ T cells obtained from BDC2.5 TCR transgenic mice. Cotransfer of these Th2-deviated $CD4^{+}$ T cells with splenic cells from newly diabetic NOD mice into $NOD.RAG^{−/−}$ mice significantly delayed the onset of diabetes. These studies suggest the alteration of DC profile and function by mATG may skew the Th1/Th2 balance in vivo and through such actions, represent an additional novel mechanism by which this agent provides its beneficial activities.
Ending Page	4615
Page Count	8
Starting Page	4608
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.0713269
Journal	The Journal of Immunology
Issue Number	8
Volume Number	182
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2009-04-15
Access Restriction	Open
Subject Keyword	Dendritic Cells Th1/th2 Cells
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology