TY - JOUR
T1 - Rabbit polyclonal anti-mouse thymocyte globulin administration alters dendritic cell profile and function in NOD mice to suppress diabetogenic responses
AU - Huang, Yanfei
AU - Parker, Matthew
AU - Xia, Changqing
AU - Peng, Ruihua
AU - Wasserfall, Clive
AU - Clarke, Tracy
AU - Wu, Lizhen
AU - Chowdhry, Tayseer
AU - Campbell-Thompson, Martha
AU - Williams, John
AU - Clare-Salzler, Michael
AU - Atkinson, Mark A.
AU - Womer, Karl L.
PY - 2009/4/15
Y1 - 2009/4/15
N2 - Anti-mouse thymocyte 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.
AB - Anti-mouse thymocyte 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.
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U2 - 10.4049/jimmunol.0713269
DO - 10.4049/jimmunol.0713269
M3 - Article
C2 - 19342635
AN - SCOPUS:65249149784
SN - 0022-1767
VL - 182
SP - 4608
EP - 4615
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -