OR.49. Dexamethasone Treated Monocyte-dendritic Cells from Latex Allergy Patients Induce Tolerance to the Major Allergen Hev b 5

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Abstracts

Moreover, CVID B-cells had a markedly reduced capacity to differentiate 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 our data), from our data we conclude that the inability of CVID CD21low B-cells to differentiate is due to their reduced proliferative potential. The behavior of CD21low B-cells in CVID might resemble that observed in “replicatively senescent” cells. doi:10.1016/j.clim.2009.03.058

Dynamic APCs Saturday, June 13 2:45 pm–4:45 pm OR.47. Impact of Organ Stromal Cells on Antigen-presenting Cell Development Lina 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, but hepatocytes transplants are acutely rejection, suggesting a role of NPC in protecting parenchymal cells. We have shown potent immune suppressive activity of hepatic stellate cells (HSC). Cotransplant with HSC effectively protected islet allografts from rejection, associated with marked expansion of Foxp3bsN+. doi:10.1016/j.clim.2009.03.059

OR.48. Identifying and Characterizing the Signal Transduction Pathways in Glatiramer Acetate (GA, Copolymer-1, Copaxone ®)-Induced Type II Monocytes Differentiation Nicolas Molnarfi, Thomas Prod'homme, Martin Weber, Scott Zamvil. University of California, San Francisco, San Francisco, CA Objective: To examine the signaling pathways that participate in GA-induced differentiation of type II antigen presenting cells (APC). Background: GA treatment promoted development of type II monocytes, characterized by increased secretion of TGFβ-1, diminished production of TNF, and reduced signal transducer and activator of transcription 1 (STAT1) signaling in response to lipopolysaccharide (LPS) stimulation. Data indicate that type II monocytes are responsible for T cell immune modulation associated with GA treatment. Signaling mechanisms responsible for type II monocyte differentiation by GA have not yet been elucidated. Results: While GA triggered rapid phosphatidylinositide-3 kinase (PI3K) activation in monocytes, it failed to elicit cyclic adenosine 3′,5′ monophosphate (cAMP) induction, suggesting a potential receptor-associated mechanism of action of GA in type II differentiation. Separately, we demonstrated that decreased STAT1 activation correlates with a reduced LPS-induced IFN-β production

These results were confirmed by our observations that GA treatment inhibited p38 mitogen activated protein kinase (MAPK) phosphorylation and downstream DNA-binding of Activating Transcription Factor-2 (ATF-2), which transcriptional activity is involved in IFN-β expression. Using myeloid differentiation protein 88 (MyD88)-deficient monocytes, as well as MyD88-dependent and independent stimuli, we further ruled out the contribution of MyD88-dependent pathway in type II differentiation. Conclusion/Relevance: These results emphasize the role of PI3K and MAPK signaling pathways in type II monocyte differentiation. This study is highly relevant to multiple sclerosis (MS) therapy as it may provide insight leading to the development of reagents that may promote type II monocyte differentiation more effectively than GA. doi:10.1016/j.clim.2009.03.060

OR.49. Dexamethasone Treated Monocyte-dendritic Cells from Latex Allergy Patients Induce Tolerance to the Major Allergen Hev b 5 Alejandro Escobar1, María Antonieta Guzmán1, Juan Aguillon2. 1 Clinical Hospital of the University of Chile, Santiago, Chile; 2 University of Chile, Santiago, Chile Natural rubber latex allergy is a significant problem both for health care workers and for children with complex medical and surgical conditions that require multiple surgical interventions. Current subcutaneous and sublingual immunotherapy schedules have been tested for treatment of latex allergy with evidence of efficacy but the risks of adverse events are high. To day the immunotherapeutical use of tolerogenic dendritic cells has been explored in preclinical and animal models studies to autoimmune and allergic diseases. In this work, we demonstrated that monocyte derived dendritic cells treated with dexamethasone from latex allergy patients differentiate into a subset of tolerogenic dendritic cells, characterized by low expression of MHC class II, CD40, CD83, CD80 and CD86 molecules, high endocytosis capability, IL-12 low / IL-10 high cytokine profile and low alloantigen proliferation potential. Furthermore, dexamethasone treated dendritic cells were able to inhibit both specific proliferation of Hev b 5 latex specific T-cell lines and the production of Hev b 5 specific IgE antibodies. This work provides in vitro data for an innovative immunomodulatory approach that may be soon translated to the clinic for latex sensitised or allergic subjects. doi:10.1016/j.clim.2009.03.061

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