activity of agonists of TLR7 and TLR9 in preclinical studies.In the present studies, we have evaluated two antagonistcandidates for their anti-inflammatory activity in ovalbumin(OVA)-induced inflammation in mice. BALB/c mice sensi-tized and challenged with OVA showed increased levels ofIgE in the serum and Th2-type cytokines, IL-5 and IL-13, inspleen cell recall response compared with naïve mice.Treatment of OVA-sensitized mice with subcutaneous admin-istration of TLR antagonists, at the same time as OVA-sensitization (prevention model) or twelve days after OVA-sensitization (treatment model), reduced serum levels of IgEand suppressed IL-5 and IL-13 production in the spleen cellscompared with mice not treated with antagonists. Moreover,the treatment of OVA-sensitized mice with antagonists didnot result in the induction of Th1-type IFN-gamma and IgG2aproduction in either the prevention or the treatment model.Histology of lung tissues showed decreased levels of in-flammatory cells and mucin secreting cells in antagonisttreated mice in both prevention and treatment models. Theresults of the present studies suggest that TLR7 and TLR9antagonists have anti-inflammatory responses in a mousemodel of OVA-induced inflammation and may have poten-tial as immunotherapeutic agents against inflammatorydiseases.

doi:10.1016/j.clim.2008.03.059

OR.54. Outcomes of 20 Patients Treated withAnti-CD6-T-cell Depleted, Non-conditionedHematopoietic Stem Cell Transplantation for SevereCombined Immunodeficiency (SCID) includingOmenn SyndromeNiraj Patel,1 Javier Chinen,1 Howard Rosenblatt,1 Imelda C.Hanson,1 Betty Brown,1 Jerome Ritz,2 William Shearer.11Baylor College of Medicine, Texas Children's Hospital,Houston, TX;

2Dana-Farber Cancer Institute, Harvard

Medical School, Boston, MD

Background: Monoclonal anti-CD6 antibody has beenused to deplete mature donor T cells to reduce the degreeof graft-versus-host disease (GvHD) in human stem celltransplantation (HSCT), principally for leukemias. Wereport the long-term outcome of 20 SCID children (medianage at transplant 6.5 [range 0.5-145] mo, 12 with seriousinfection) treated with bone marrow (6 [0.8-18.8]×108

cells/Kg) from mismatched related donors (MMRD) and of 5SCID children (median age at transplant 1.8 [0.5-5.0] mo, 1with serious infection) given unmanipulated bone marrowfrom matched related donors (MRD). None of these patientsreceived myeloablative conditioning or additional GvHDprophylaxis. Methods: In 2007 we reviewed the medicalrecords of these 25 SCID patients (HSCT between 1982 and1995) at our center and patient relocation centers (LosAngeles, CA [R Stiehm], Denver, CO [P Hauk], Kansas City,MO [J Portnoy]). Results: 20 MMRD patients: 12 engrafted;10 survive at a median age of 16.7 [12.7-24.5] yr; 4 havechronic GvHD (lung, intestine, skin); 6 require intravenousimmunoglobulin (IVIG) and 9 attend(ed) school or college.Median survival after HSCT of those who expired was 5 [1-200] mo. Two of these had chronic GvHD and 2 developed

post-transplant lymphoproliferative disease. 5 MRDpatients: 5 engrafted; 5 survive at median age 23.3 [19.4-26.5] yr; 1 has chronic GvHD (lung, skin); 1 requires IVIG;and 4 attend(ed) school or college. Conclusions: Using anti-CD6-T-cell antibody depleted MMRD marrow in critically illSCID patients resulted in an overall 50% long-term survival ofpatients (83% survival of those engrafted). The principalbarriers to long-term survival were delay in diagnosis of SCID,pre-HSCT life-threatening infection, failure to engraft, andchronic GvHD. Educational goals were achieved in 90% of thesurvivors.

doi:10.1016/j.clim.2008.03.060

Drivers & Suppressors of AutoimmunitySaturday, June 72:45 pm–4:45 pm

OR.55. Fas Mutated Dendritic Cells Derived fromNOD-lpr/lpr Prevent Autoimmune DiabetesMinoru Kishi, Hisafumi Yasuda, Mami Kameno, Takashi Arai,Yasuyo Okumachi, Midori Kurohara, Hiroaki Moriyama,Koichi Yokono, Masao Nagata. Kobe University, Kobe,Japan

Dendritic cell (DC) is a most potent professional antigenpresenting cell (APC) and recognized to serve as a centralmediator of T cell-based immunity. NODlpr/lpr mice withFas mutation don't develop diabetes. Previously wereported administration of anti-FasL antibody into NODmice during 2–4 wk of age completely prevented NODdiabetes. These results suggest a critical role of Fas-FasLinteraction in the initiation of autoimmune NOD diabetes.We generated Fas-mutated NODlpr/lpr bone marrow-derivedDCs (lpr-BMDCs) and examined the preventive effect onautoimmune diabetes via the modification of Fas-FasLpathway in young NOD mice. lpr-BMDCs were generatedafter 6 days of culture with GM-CSF and IL-4. Flowcytometric analysis showed a lower expression of Fas andsome co-stilumatory molucules on lpr-BMDCs than on NOD-BMDCs. In allo-MLR, lpr-BMDCs had a lower capacity toproliferate T cells than NOD-BMDCs, resulting in lowerproduction of IFN-γ. Intraperitoneal injection with lpr-BMDCs at 2-4 wk of age completely prevented overtdiabetes onset at 35 wk (diabetes incidence; 0%, n=20), ascompared with PBS (80%, n=13). Histological findingsrevealed mild insulitis in lpr-BMDC-transferred mice.Although neither CD4+CD25+, CD8+CD122+, nor NKT cellpopulation was not increased in splenocytes from trans-ferred mice, delayed onset of diabetes was induced by co-transfer with splenocytes from transferred miceand diabetic splenocytes, compared with diabetic spleno-cytes alone. Taken together, Fas-mutated DCs might betolerogenic to autoimmune diabetes by inducing regulatorycells.

doi:10.1016/j.clim.2008.03.061

S23Abstracts