PMID- 19342635 OWN - NLM STAT- MEDLINE DCOM- 20090423 LR - 20211020 IS - 1550-6606 (Electronic) IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 182 IP - 8 DP - 2009 Apr 15 TI - Rabbit polyclonal mouse antithymocyte globulin administration alters dendritic cell profile and function in NOD mice to suppress diabetogenic responses. PG - 4608-15 LID - 10.4049/jimmunol.0713269 [doi] AB - 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. FAU - Huang, Yanfei AU - Huang Y AD - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21204, USA. FAU - Parker, Matthew AU - Parker M FAU - Xia, Changqing AU - Xia C FAU - Peng, Ruihua AU - Peng R FAU - Wasserfall, Clive AU - Wasserfall C FAU - Clarke, Tracy AU - Clarke T FAU - Wu, Lizhen AU - Wu L FAU - Chowdhry, Tayseer AU - Chowdhry T FAU - Campbell-Thompson, Martha AU - Campbell-Thompson M FAU - Williams, John AU - Williams J FAU - Clare-Salzler, Michael AU - Clare-Salzler M FAU - Atkinson, Mark A AU - Atkinson MA FAU - Womer, Karl L AU - Womer KL LA - eng GR - K08DK66319/DK/NIDDK NIH HHS/United States GR - K08 DK066319-04/DK/NIDDK NIH HHS/United States GR - DK063422/DK/NIDDK NIH HHS/United States GR - K08 DK066319-03/DK/NIDDK NIH HHS/United States GR - R33 DK063422/DK/NIDDK NIH HHS/United States GR - K08 DK066319/DK/NIDDK NIH HHS/United States GR - 394288/PHS HHS/United States GR - P01 AI042288/AI/NIAID NIH HHS/United States GR - 394210/PHS HHS/United States GR - K08 DK066319-05/DK/NIDDK NIH HHS/United States GR - P01 AI042288-11/AI/NIAID NIH HHS/United States GR - N01 DK063422/DK/NIDDK NIH HHS/United States GR - R21 DK063422/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antilymphocyte Serum) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - Antilymphocyte Serum/*administration & dosage/*immunology/pharmacology MH - Bone Marrow/immunology MH - Cell Differentiation/immunology MH - Dendritic Cells/cytology/*drug effects/*immunology/metabolism MH - Diabetes Mellitus/*immunology MH - Female MH - Interleukin-10/biosynthesis/immunology MH - Mice MH - Mice, Inbred NOD MH - Rabbits MH - Spleen/immunology MH - Th2 Cells/immunology PMC - PMC2770841 MID - NIHMS108443 EDAT- 2009/04/04 09:00 MHDA- 2009/04/25 09:00 PMCR- 2010/04/15 CRDT- 2009/04/04 09:00 PHST- 2009/04/04 09:00 [entrez] PHST- 2009/04/04 09:00 [pubmed] PHST- 2009/04/25 09:00 [medline] PHST- 2010/04/15 00:00 [pmc-release] AID - 182/8/4608 [pii] AID - 10.4049/jimmunol.0713269 [doi] PST - ppublish SO - J Immunol. 2009 Apr 15;182(8):4608-15. doi: 10.4049/jimmunol.0713269.