PMID- 18318993 OWN - NLM STAT- MEDLINE DCOM- 20080715 LR - 20211020 IS - 1672-7681 (Print) IS - 2042-0226 (Electronic) IS - 1672-7681 (Linking) VI - 5 IP - 1 DP - 2008 Feb TI - IL-10 gene modified dendritic cells inhibit T helper type 1-mediated alloimmune responses and promote immunological tolerance in diabetes. PG - 41-6 LID - 10.1038/cmi.2008.5 [doi] AB - Dendritic cells (DCs) have the potency to regulate the outcome of autoimmunity through the modulation of immune responses. The induction of antigen specific tolerance is critical for prevention and treatment of allograft rejection. In the present study, we transfected IL-10 gene into DCs and investigated their effect on inhibition of lymphocyte activity in vitro and induction of immune tolerance on islet allograft in mice. An IDDM C57BL/6 mouse model was induced by streptozotocin. The islet cells isolated from the BALB/c mice were transplanted into the kidney capules of the model mice followed by injection of IL-10 modified DCs (mDCs). The results showed that mDCs could significantly inhibit T lymphocyte proliferation mediated by allotype cells and induce its apoptosis, whereas, unmodified DCs (umDCs) could promote the murine lymphocyte proliferation markedly. The injection of mDCs could prolong the survival of allotype islet transplanted IDDM mice. The average plasma glucose (PG) level in mDCs treated mice returned to normal within 3 days and lasted for about 2 weeks. The rejection response in control mice occurred for 5 days after transplantation. The level of IFN-gamma was lower while IL-4 was higher in mDCs treated mice than that in umDCs treated mice, which indicated that Th1/Th2 deviation occurred. Our studies suggest that IL-10 gene modified DCs can induce the immune tolerance to islet graft and prolong survival of the recipients by the inhibiting of T cell proliferation in allotype mice. FAU - Zhu, Huifen AU - Zhu H AD - Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Qiu, Wenhong AU - Qiu W FAU - Lei, Ping AU - Lei P FAU - Zhou, Wei AU - Zhou W FAU - Wen, Xue AU - Wen X FAU - He, Fengrong AU - He F FAU - Li, Li AU - Li L FAU - Dai, Hong AU - Dai H FAU - Shen, Guanxin AU - Shen G FAU - Gong, Feili AU - Gong F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Cell Mol Immunol JT - Cellular & molecular immunology JID - 101242872 RN - 0 (Blood Glucose) RN - 130068-27-8 (Interleukin-10) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Apoptosis MH - Blood Glucose/analysis MH - Cell Proliferation MH - Dendritic Cells/*immunology/metabolism MH - Diabetes Mellitus, Type 1/*immunology/metabolism/surgery MH - Glucose Tolerance Test MH - Graft Rejection MH - *Immune Tolerance MH - Interferon-gamma/biosynthesis/immunology MH - Interleukin-10/genetics/*immunology/metabolism MH - Interleukin-4/blood MH - Islets of Langerhans Transplantation/*immunology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Th1 Cells/*immunology/metabolism MH - Transfection MH - Transplantation Tolerance MH - Transplantation, Homologous PMC - PMC4072399 EDAT- 2008/03/06 09:00 MHDA- 2008/07/17 09:00 PMCR- 2008/02/01 CRDT- 2008/03/06 09:00 PHST- 2008/03/06 09:00 [pubmed] PHST- 2008/07/17 09:00 [medline] PHST- 2008/03/06 09:00 [entrez] PHST- 2008/02/01 00:00 [pmc-release] AID - cmi20085 [pii] AID - 10.1038/cmi.2008.5 [doi] PST - ppublish SO - Cell Mol Immunol. 2008 Feb;5(1):41-6. doi: 10.1038/cmi.2008.5.