Moreover, CVID B-cells had a markedly reduced capacity todifferentiate into plasmablasts upon stimulation with CpG.As normal B-cells differentiate only after a critical number(≈4) of cell divisions (Hodgkin et al., JEM 1996, and ourdata), from our data we conclude that the inability of CVIDCD21low B-cells to differentiate is due to their reducedproliferative potential. The behavior of CD21low B-cells inCVID might resemble that observed in “replicativelysenescent” cells.

doi:10.1016/j.clim.2009.03.058

Dynamic APCsSaturday, June 132:45 pm–4:45 pm

OR.47. Impact of Organ Stromal Cells onAntigen-presenting Cell DevelopmentLina Lu, Ching-Chuan Hsieh, Xiaodong Gu, Horng-Ren Yang,Lianfu Wang, John Fung, Shiguang Qian. Cleveland Clinic,Cleveland, OH

Liver allografts are spontaneously accepted in mice, buthepatocytes transplants are acutely rejection, suggesting a roleof NPC in protecting parenchymal cells. We have shown potentimmune suppressive activity of hepatic stellate cells (HSC). Co-transplant with HSC effectively protected islet allografts fromrejection, associated with marked expansion of Foxp3bsN+.

doi:10.1016/j.clim.2009.03.059

OR.48. Identifying and Characterizing the SignalTransduction Pathways in Glatiramer Acetate(GA, Copolymer-1, Copaxone ®)-Induced Type IIMonocytes DifferentiationNicolas Molnarfi, Thomas Prod'homme, Martin Weber,Scott Zamvil. University of California, San Francisco,San Francisco, CA

Objective: To examine the signaling pathways thatparticipate in GA-induced differentiation of type II antigenpresenting cells (APC). Background: GA treatment promoteddevelopment of type II monocytes, characterized byincreased secretion of TGFβ-1, diminished production ofTNF, and reduced signal transducer and activator oftranscription 1 (STAT1) signaling in response to lipopolysac-charide (LPS) stimulation. Data indicate that type II mono-cytes are responsible for T cell immune modulationassociated with GA treatment. Signaling mechanisms respon-sible for type II monocyte differentiation by GA have not yetbeen elucidated. Results: While GA triggered rapid phospha-tidylinositide-3 kinase (PI3K) activation in monocytes, itfailed to elicit cyclic adenosine 3′,5′ monophosphate (cAMP)induction, suggesting a potential receptor-associatedmechanism of action of GA in type II differentiation.Separately, we demonstrated that decreased STAT1 activa-tion correlates with a reduced LPS-induced IFN-β production

These results were confirmed by our observations that GAtreatment inhibited p38 mitogen activated protein kinase(MAPK) phosphorylation and downstream DNA-binding ofActivating Transcription Factor-2 (ATF-2), which transcrip-tional activity is involved in IFN-β expression. Using myeloiddifferentiation protein 88 (MyD88)-deficient monocytes, aswell as MyD88-dependent and independent stimuli, wefurther ruled out the contribution of MyD88-dependentpathway in type II differentiation. Conclusion/Relevance:These results emphasize the role of PI3K and MAPK signalingpathways in type II monocyte differentiation. This study ishighly relevant to multiple sclerosis (MS) therapy as it mayprovide insight leading to the development of reagents thatmay promote type II monocyte differentiation more effec-tively than GA.

doi:10.1016/j.clim.2009.03.060

OR.49. Dexamethasone Treated Monocyte-dendriticCells from Latex Allergy Patients Induce Toleranceto the Major Allergen Hev b 5Alejandro Escobar1,MaríaAntonietaGuzmán1, JuanAguillon2.1 Clinical Hospital of the University of Chile, Santiago, Chile;2 University of Chile, Santiago, Chile

Natural rubber latex allergy is a significant problem bothfor health care workers and for children with complexmedical and surgical conditions that require multiplesurgical interventions. Current subcutaneous and sublingualimmunotherapy schedules have been tested for treatmentof latex allergy with evidence of efficacy but the risks ofadverse events are high. To day the immunotherapeuticaluse of tolerogenic dendritic cells has been explored inpreclinical and animal models studies to autoimmune andallergic diseases. In this work, we demonstrated thatmonocyte derived dendritic cells treated with dexametha-sone from latex allergy patients differentiate into a subsetof tolerogenic dendritic cells, characterized by low expres-sion of MHC class II, CD40, CD83, CD80 and CD86 molecules,high endocytosis capability, IL-12 low / IL-10 high cytokineprofile and low alloantigen proliferation potential. Further-more, dexamethasone treated dendritic cells were able toinhibit both specific proliferation of Hev b 5 latex specificT-cell lines and the production of Hev b 5 specific IgEantibodies. This work provides in vitro data for aninnovative immunomodulatory approach that may be soontranslated to the clinic for latex sensitised or allergicsubjects.

doi:10.1016/j.clim.2009.03.061

OR.50. in vitro Modulation of InfluenzaVirus-specific CD4+T cell Responses via Dectin-1Expressed on Human Dendritic Cell SubsetsLing Ni, Xiao-Hua Li, Ingrid Gayet, Peter Klucar, Dapeng Li,Melissa Dullaers, Sandra Zurawski, Gerard Zurawski,Jacques Banchereau, SangKon Oh. Baylor ResearchInstitute, Dallas, TX

S22 Abstracts